library(dplyr)
library(knitr)
select_top_genes <- function(inversion,type){
trans <- sig_genes_trans[which(sig_genes_trans$Inversion==inversion & sig_genes_trans$Type_analysis==type),]
selecttrans <- data.frame(Inversion=character(),
Type_analysis=character(),
Transcript=character(),
Location=character(),
Gene_Symbol=character(),
model=character(),
adj.p.value=numeric(),
DiffLevene_logFC=numeric(),
stringsAsFactors=FALSE)
for (transcript in trans$Transcript){
transcriptsDF <- trans[which(trans$Transcript==transcript),]
bestmodel <- transcriptsDF[which.min(transcriptsDF$adj.p.value),]
selecttrans <- rbind(selecttrans,bestmodel)
}
selecttrans <- selecttrans %>% distinct()
return(selecttrans)
}
select_top_cpgs <- function(inversion,type){
methy <- sig_cpgs_methy[which(sig_cpgs_methy$Inversion==inversion & sig_cpgs_methy$Type_analysis==type),]
selectmethy <- data.frame(Inversion=character(),
Type_analysis=character(),
CpG=character(),
Location=character(),
Gene_Symbol=character(),
model=character(),
adj.p.value=numeric(),
DiffLevene_logFC=numeric(),
stringsAsFactors=FALSE)
for (cpg in methy$CpG){
cpgsDF <- methy[which(methy$CpG==cpg),]
bestmodel <- cpgsDF[which.min(cpgsDF$adj.p.value),]
selectmethy <- rbind(selectmethy,bestmodel)
}
selectmethy <- selectmethy %>% distinct()
return(selectmethy)
}
Table 1 shows the associations between polymorphic inversions and obesity-related traits with a p-value below 0.0227. In the case of neurological traits, Table 2 displays the associations with a p-value below 0.01.
| Phenotype | Phenotype_abrev | Inversion | model | p.value |
|---|---|---|---|---|
| hs_chol_cperc_None_v2 | Total Cholesterol | 8p23.1 | Dominant | 0.0197885 |
| hs_chol_cperc_None_v2 | Total Cholesterol | 8p23.1 | Additive | 0.0091123 |
| hs_phospho_c_None | Phospholipids | 8p23.1 | Dominant | 0.0197029 |
| hs_phospho_cperc_None_v2 | Phospholipids | 8p23.1 | Dominant | 0.0197029 |
| hs_totchol_c_None | Total Cholesterol | 8p23.1 | Dominant | 0.0197885 |
| hs_totchol_c_None | Total Cholesterol | 8p23.1 | Additive | 0.0091123 |
| e3_bwc_None | Birth weight | 8p23.1 | Recessive | 0.0107270 |
| e3_pi_None | Ponderal index | 8p23.1 | Recessive | 0.0135604 |
| hs_creatinine_c_None | Creatinine | 16p11.2 | Dominant | 0.0156135 |
| hs_creatinine_cg_None | Creatinine | 16p11.2 | Dominant | 0.0156135 |
| Phenotype | Phenotype_abrev | Inversion | model | p.value |
|---|---|---|---|---|
| hs_Esc_AD | NA | 16p11.2 | Recessive | 0.0085207 |
| hs_nhitcolors1 | number of hits colors 1-back | 16p11.2 | Dominant | 0.0063459 |
| hs_nfacolors1 | number of false alarms colors 1-back | 17q21.31 | Additive | 0.0095820 |
| hs_nmisscolors1 | number of miss colors 1-back | 17q21.31 | Dominant | 0.0032456 |
| hs_nmisscolors1 | number of miss colors 1-back | 17q21.31 | Additive | 0.0031775 |
| hs_nhitcolors3 | number of hits colors 3-back | 17q21.31 | Additive | 0.0079295 |
| hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 17q21.31 | Dominant | 0.0036305 |
| hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 17q21.31 | Additive | 0.0018287 |
| hs_dcolors1 | detectability colors 1-back | 17q21.31 | Dominant | 0.0042137 |
| hs_dcolors1 | detectability colors 1-back | 17q21.31 | Additive | 0.0027919 |
| hs_accuracy_numeros3 | Percentage of correct responses (hits and correct rejections) numbers 3-back | 17q21.31 | Recessive | 0.0022171 |
| hs_dnumeros3 | detectability numbers 3-back | 17q21.31 | Recessive | 0.0008315 |
| hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 17q21.31 | Dominant | 0.0018789 |
| hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 17q21.31 | Additive | 0.0015241 |
Inversion 8p23.1
The significant MDE genes for inversion 8p23.1 are shown in Table 3. Figures 1, 2, 3, and 4 include panels of box-plots illustrating the effect of inversion status on the gene expression. Finally, the enrichment analysis of these genes has been performed and the results are presented in Figure 5.
| Inversion | Type_analysis | Transcript | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|
| 8p23.1 | Mean | TC08000087.hg.1 | chr8:11351510-11422113 | BLK | additive | 0.0000000 | -0.1227452 |
| 8p23.1 | Mean | TC08000093.hg.1 | chr8:11653082-11696818 | FDFT1 | additive | 0.0000000 | 0.0832526 |
| 8p23.1 | Mean | TC08000975.hg.1 | chr8:11278972-11324276 | FAM167A | additive | 0.0000000 | 0.0762627 |
| 8p23.1 | Mean | TC08000937.hg.1 | chr8:8095196-8102189 | ALG1L13P | additive | 0.0000000 | 0.0875426 |
| 8p23.1 | Mean | TC08000056.hg.1 | chr8:8086092-8102387 | FAM86B3P | additive | 0.0000000 | -0.0303383 |
| 8p23.1 | Mean | TC08000099.hg.1 | chr8:12051976-12053789 | FAM85A | additive | 0.0000000 | 0.1051436 |
| 8p23.1 | Mean | TC08000067.hg.1 | chr8:9046509-9060364 | BC017578 | additive | 0.0000000 | 0.0376679 |
| 8p23.1 | Mean | TC08002596.hg.1 | chr8:12294522-12424423 | LOC100506990 | additive | 0.0000000 | 0.0464301 |
| 8p23.1 | Mean | TC08001804.hg.1 | chr8:11973291-12482364 | LOC100506990;FAM66D;FAM66A | additive | 0.0000000 | 0.0358563 |
| 8p23.1 | Mean | TC08000085.hg.1 | chr8:11188397-11189717 | SLC35G5 | additive | 0.0000000 | -0.0532857 |
| 8p23.1 | Mean | TC08000988.hg.1 | chr8:12039605-12051642 | FAM86B1 | additive | 0.0000000 | -0.0204385 |
| 8p23.1 | Mean | TC08000091.hg.1 | chr8:11627172-11644855 | NEIL2 | additive | 0.0000002 | 0.0222975 |
| 8p23.1 | Mean | TC08000071.hg.1 | chr8:9911778-10286401 | MSRA | additive | 0.0000032 | -0.0182060 |
| 8p23.1 | Mean | TC08000995.hg.1 | chr8:12282913-12293915 | FAM86B2;FAM86B1 | additive | 0.0000068 | -0.0184390 |
| 8p23.1 | Mean | TC08000063.hg.1 | chr8:8859657-8974256 | ERI1 | additive | 0.0000144 | 0.0185050 |
| 8p23.1 | Mean | TC08000938.hg.1 | chr8:8175258-8244008 | SGK223 | additive | 0.0000190 | 0.0357897 |
| 8p23.1 | Mean | TC08000935.hg.1 | chr8:7992174-8085385 | FAM85B | additive | 0.0002706 | 0.0300686 |
| 8p23.1 | Mean | TC08002222.hg.1 | chr8:10980891-10982327 | C8orf15 | recessive | 0.0004446 | 0.0690433 |
| 8p23.1 | Mean | TC08002231.hg.1 | chr8:12282231-12282893 | AK308439 | additive | 0.0024369 | -0.0359307 |
| 8p23.1 | Mean | TC08000069.hg.1 | chr8:9413422-9639856 | TNKS | additive | 0.0036524 | -0.0115602 |
| 8p23.1 | Mean | TC08000994.hg.1 | chr8:12282231-12282893 | AK308439 | additive | 0.0077124 | -0.0323173 |
Figure 1: Box-plot representation for the mean differentially expressed genes in inversion 8p23.1 (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 2: Box-plot representation for the mean differentially expressed genes in inversion 8p23.1 (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 3: Box-plot representation for the mean differentially expressed genes in inversion 8p23.1 (3)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 4: Box-plot representation for the mean differentially expressed genes in inversion 8p23.1 (4)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 5: Enrichment analysis results for the mean differential expressed (DE) genes for inversion 8p23.1
The colour depends on the p-value adjusted and the size of the dot indicates the number of counts. A) Results using KEGG database; B) Results using DisGeNET database; c) Results using GO database.
Inversion 16p11.2
In the case of the 16p11.2 region, Table 4 reveals the MDE genes, and Figures 6, 7, 8 show the distribution of the gene expression according to the inversion status. The results of the enrichment analysis are displayed in Figure 9.
| Inversion | Type_analysis | Transcript | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|
| 16p11.2 | Mean | TC16000994.hg.1 | chr16:28853732-28857729 | TUFM;MIR4721 | additive | 0.0000000 | 0.1590659 |
| 16p11.2 | Mean | TC16000303.hg.1 | chr16:28565247-28603111 | CCDC101 | additive | 0.0000000 | -0.1367914 |
| 16p11.2 | Mean | TC16000314.hg.1 | chr16:28986093-29002104 | LAT;SPNS1 | additive | 0.0000000 | 0.0461986 |
| 16p11.2 | Mean | TC16000986.hg.1 | chr16:28390900-28437775 | EIF3CL;EIF3C | dominant | 0.0000000 | 0.2095409 |
| 16p11.2 | Mean | TC16000305.hg.1 | chr16:28699879-28747053 | EIF3C;EIF3CL | additive | 0.0000000 | 0.1551929 |
| 16p11.2 | Mean | TC16000300.hg.1 | chr16:28303840-28335170 | SBK1 | additive | 0.0000000 | -0.0644445 |
| 16p11.2 | Mean | TC16000991.hg.1 | chr16:28616903-28634907 | SULT1A1 | additive | 0.0000035 | -0.0657185 |
| 16p11.2 | Mean | TC16002064.hg.1 | chr16:28477974-28503623 | CLN3 | recessive | 0.0001750 | 0.0252059 |
| 16p11.2 | Mean | TC16000306.hg.1 | chr16:28763108-29064044 | NPIPL1;NPIPB9 | additive | 0.0020281 | 0.0197922 |
| 16p11.2 | Mean | TC16000985.hg.1 | chr16:28353876-28374829 | NPIPL1;NPIPB6 | additive | 0.0056078 | 0.0183324 |
| 16p11.2 | Mean | TC16000990.hg.1 | chr16:28603264-28608430 | SULT1A2 | dominant | 0.0036653 | -0.0408426 |
| 16p11.2 | Mean | TC16002063.hg.1 | chr16:28467693-28481868 | NPIPB7;NPIPL1 | additive | 0.0131460 | 0.0178750 |
| 16p11.2 | Mean | TC16000304.hg.1 | chr16:28648975-28670003 | NPIPB8;NPIPL1 | dominant | 0.0198395 | 0.0254312 |
| 16p11.2 | Mean | TC16001830.hg.1 | chr16:29114978-29119032 | AK075019 | additive | 0.0217447 | 0.0195208 |
| 16p11.2 | Mean | TC16000307.hg.1 | chr16:28814097-28829149 | AK125489 | dominant | 0.0108139 | -0.0333196 |
Figure 6: Box-plot representation for the mean differentially expressed genes in inversion 16p11.2 (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 7: Box-plot representation for the mean differentially expressed genes in inversion 16p11.2 (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 8: Box-plot representation for the mean differentially expressed genes in inversion 16p11.2 (3)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 9: Enrichment analysis results for the mean differentially expressed (DE) genes for inversion 16p11.2
The colour depends on the p-value adjusted and the size of the dot indicates the number of counts. A) Results using KEGG database; B) Results using DisGeNET database; c) Results using GO database.
Inversion 17q21.31
The polymorphic inversion 17q21.31 changes the mean expression of the genes that appear in Table 5 and in Figures 10 and 11. The enrichment analysis did not revealed any overrepresented function or disease.
| Inversion | Type_analysis | Transcript | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|
| 17q21.31 | Mean | TC17001604.hg.1 | chr17:43590734-43593064 | AX747150;LRRC37A4P | dominant | 0.0000201 | 0.1043619 |
| 17q21.31 | Mean | TC17000597.hg.1 | chr17:44370099-44415160 | LRRC37A | dominant | 0.0000083 | 0.0749635 |
| 17q21.31 | Mean | TC17002671.hg.1 | chr17:43593073-43593494 | DQ588732 | additive | 0.0007577 | 0.0580581 |
| 17q21.31 | Mean | TC17000599.hg.1 | chr17:44590076-44633016 | LRRC37A2 | dominant | 0.0000479 | 0.0853964 |
| 17q21.31 | Mean | TC17001605.hg.1 | chr17:43593073-43593494 | DQ588732 | additive | 0.0009355 | 0.0548442 |
| 17q21.31 | Mean | TC17001603.hg.1 | chr17:43578684-43597889 | LRRC37A4P | recessive | 0.0001806 | -0.1378019 |
| 17q21.31 | Mean | TC17001608.hg.1 | chr17:43677491-43679748 | LOC644172 | recessive | 0.0066951 | -0.1062447 |
| 17q21.31 | Mean | TC17000596.hg.1 | chr17:44270939-44274089 | KANSL1-AS1 | dominant | 0.0134399 | 0.0531628 |
Figure 10: Box-plot representation for the mean differentially expressed genes in inversion 17q21.31 (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 11: Box-plot representation for the mean differentially expressed genes in inversion 17q21.31 (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Inversion 8p23.1
The MDM CpG sites for inversion 8p23.1 are shown in Table 6 and their respective genes are enriched in functions revealed in Figure 12.
| Inversion | Type_analysis | CpG | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|
| 8p23.1 | Mean | cg12568669 | chr8:11666485 | FDFT1 | additive | 0.0000000 | -0.0611847 |
| 8p23.1 | Mean | cg11548083 | chr8:10208156 | MSRA | additive | 0.0000000 | 0.0282089 |
| 8p23.1 | Mean | cg12940923 | chr8:10282607 | MSRA | additive | 0.0000000 | 0.0310833 |
| 8p23.1 | Mean | cg01383082 | chr8:11323474 | FAM167A | additive | 0.0000000 | -0.0294784 |
| 8p23.1 | Mean | cg02711665 | chr8:11664728 | FDFT1 | additive | 0.0000000 | 0.0264331 |
| 8p23.1 | Mean | cg11465442 | chr8:11832261 | DEFB136 | additive | 0.0000000 | 0.0222735 |
| 8p23.1 | Mean | cg12395012 | chr8:11607386 | GATA4 | additive | 0.0000000 | -0.0282734 |
| 8p23.1 | Mean | cg20987067 | chr8:8747297 | MFHAS1 | additive | 0.0000000 | 0.0229878 |
| 8p23.1 | Mean | cg20449619 | chr8:10581784 | SOX7 | additive | 0.0000000 | 0.0314587 |
| 8p23.1 | Mean | cg02319733 | chr8:10282549 | MSRA | additive | 0.0000000 | 0.0153225 |
| 8p23.1 | Mean | cg08265495 | chr8:11212668 | TDH | additive | 0.0000000 | 0.0325432 |
| 8p23.1 | Mean | cg06620390 | chr8:10192943 | MSRA | additive | 0.0000000 | 0.0209409 |
| 8p23.1 | Mean | cg00629382 | chr8:10268916 | MSRA | additive | 0.0000000 | 0.0179638 |
| 8p23.1 | Mean | cg08841257 | chr8:10191002 | MSRA | additive | 0.0000000 | 0.0249395 |
| 8p23.1 | Mean | cg02771117 | chr8:11279352 | FAM167A;C8orf12 | additive | 0.0000000 | 0.0466767 |
| 8p23.1 | Mean | cg13601595 | chr8:10468038 | RP1L1 | additive | 0.0000000 | -0.0143857 |
| 8p23.1 | Mean | cg21701351 | chr8:11374773 | BLK | additive | 0.0000000 | -0.0266353 |
| 8p23.1 | Mean | cg10596361 | chr8:10907750 | XKR6 | additive | 0.0000000 | 0.0274953 |
| 8p23.1 | Mean | cg20497631 | chr8:8647440 | MFHAS1 | additive | 0.0000000 | 0.0245341 |
| 8p23.1 | Mean | cg21725652 | chr8:10918152 | XKR6 | additive | 0.0000000 | 0.0259479 |
| 8p23.1 | Mean | cg15426459 | chr8:11813211 | additive | 0.0000000 | 0.0248835 | |
| 8p23.1 | Mean | cg00184457 | chr8:8946301 | additive | 0.0000000 | 0.0273532 | |
| 8p23.1 | Mean | cg05460571 | chr8:8630364 | additive | 0.0000000 | 0.0124244 | |
| 8p23.1 | Mean | cg21915799 | chr8:10282809 | MSRA | additive | 0.0000000 | 0.0209622 |
| 8p23.1 | Mean | cg03399933 | chr8:11205972 | TDH | additive | 0.0000000 | -0.0293170 |
| 8p23.1 | Mean | cg02840367 | chr8:11660030 | FDFT1 | additive | 0.0000000 | -0.0421582 |
| 8p23.1 | Mean | cg27000590 | chr8:8182003 | PRAGMIN | additive | 0.0000000 | -0.0175409 |
| 8p23.1 | Mean | cg12840336 | chr8:11422730 | additive | 0.0000000 | -0.0266457 | |
| 8p23.1 | Mean | cg14919250 | chr8:10917293 | XKR6 | additive | 0.0000000 | 0.0254535 |
| 8p23.1 | Mean | cg16038868 | chr8:10192619 | MSRA | additive | 0.0000000 | 0.0144216 |
| 8p23.1 | Mean | cg01601443 | chr8:10581988 | SOX7 | additive | 0.0000000 | 0.0172787 |
| 8p23.1 | Mean | cg04654363 | chr8:8581213 | additive | 0.0000000 | -0.0121287 | |
| 8p23.1 | Mean | cg03533216 | chr8:11206009 | TDH | additive | 0.0000000 | -0.0187243 |
| 8p23.1 | Mean | cg16810626 | chr8:11594003 | GATA4 | additive | 0.0000000 | 0.0331651 |
| 8p23.1 | Mean | cg16331727 | chr8:11630219 | NEIL2 | additive | 0.0000000 | -0.0240012 |
| 8p23.1 | Mean | cg20009332 | chr8:10489118 | RP1L1 | additive | 0.0000000 | 0.0162381 |
| 8p23.1 | Mean | cg05753693 | chr8:10192930 | MSRA | additive | 0.0000000 | 0.0102163 |
| 8p23.1 | Mean | cg06819296 | chr8:10982668 | XKR6 | additive | 0.0000000 | -0.0120234 |
| 8p23.1 | Mean | cg14257676 | chr8:10192642 | MSRA | additive | 0.0000000 | 0.0132926 |
| 8p23.1 | Mean | cg04989185 | chr8:9790928 | additive | 0.0000000 | -0.0199113 | |
| 8p23.1 | Mean | cg18303581 | chr8:8239485 | PRAGMIN | additive | 0.0000000 | 0.0106966 |
| 8p23.1 | Mean | cg10597661 | chr8:8256332 | additive | 0.0000000 | 0.0117799 | |
| 8p23.1 | Mean | cg00074818 | chr8:8560427 | CLDN23 | additive | 0.0000000 | 0.0150779 |
| 8p23.1 | Mean | cg09141662 | chr8:11206023 | TDH | additive | 0.0000000 | -0.0131885 |
| 8p23.1 | Mean | cg12792075 | chr8:12244565 | FAM66A | dominant | 0.0000000 | 0.0722159 |
| 8p23.1 | Mean | cg00569813 | chr8:8483549 | additive | 0.0000000 | 0.0093748 | |
| 8p23.1 | Mean | cg11269159 | chr8:9788745 | additive | 0.0000000 | -0.0120478 | |
| 8p23.1 | Mean | cg26288502 | chr8:10421582 | additive | 0.0000000 | -0.0130067 | |
| 8p23.1 | Mean | cg10657228 | chr8:10386222 | T-SP1 | additive | 0.0000000 | -0.0264181 |
| 8p23.1 | Mean | cg27127887 | chr8:11831823 | DEFB136 | additive | 0.0000000 | 0.0111173 |
| 8p23.1 | Mean | cg17475643 | chr8:10261972 | MSRA | additive | 0.0000000 | -0.0106970 |
| 8p23.1 | Mean | cg09528494 | chr8:11338675 | additive | 0.0000000 | 0.0107421 | |
| 8p23.1 | Mean | cg02520399 | chr8:8168661 | additive | 0.0000000 | 0.0118909 | |
| 8p23.1 | Mean | cg16513326 | chr8:10877312 | XKR6 | additive | 0.0000000 | 0.0090250 |
| 8p23.1 | Mean | cg06671706 | chr8:8559999 | CLDN23 | additive | 0.0000000 | 0.0281511 |
| 8p23.1 | Mean | cg14329976 | chr8:11627812 | NEIL2 | additive | 0.0000000 | 0.0209233 |
| 8p23.1 | Mean | cg11302791 | chr8:10635419 | PINX1 | additive | 0.0000000 | -0.0184717 |
| 8p23.1 | Mean | cg18237548 | chr8:8860050 | ERI1 | additive | 0.0000000 | -0.0154080 |
| 8p23.1 | Mean | cg06240162 | chr8:11142829 | MTMR9 | additive | 0.0000000 | 0.0138272 |
| 8p23.1 | Mean | cg22799963 | chr8:11536778 | additive | 0.0000000 | 0.0115425 | |
| 8p23.1 | Mean | cg23217680 | chr8:9029456 | additive | 0.0000000 | -0.0182175 | |
| 8p23.1 | Mean | cg10039590 | chr8:8859974 | ERI1 | additive | 0.0000000 | -0.0097582 |
| 8p23.1 | Mean | cg26075742 | chr8:10753237 | additive | 0.0000000 | 0.0093203 | |
| 8p23.1 | Mean | cg01273802 | chr8:10871371 | XKR6 | additive | 0.0000000 | 0.0085097 |
| 8p23.1 | Mean | cg27280535 | chr8:8746679 | MFHAS1 | additive | 0.0000000 | 0.0112203 |
| 8p23.1 | Mean | cg16871763 | chr8:11537909 | additive | 0.0000000 | 0.0096141 | |
| 8p23.1 | Mean | cg13293535 | chr8:11597251 | GATA4 | additive | 0.0000000 | -0.0277988 |
| 8p23.1 | Mean | cg11784887 | chr8:8729819 | MFHAS1 | additive | 0.0000000 | -0.0135406 |
| 8p23.1 | Mean | cg16232071 | chr8:10907718 | XKR6 | additive | 0.0000000 | -0.0140330 |
| 8p23.1 | Mean | cg01558037 | chr8:10772570 | XKR6 | additive | 0.0000000 | 0.0125076 |
| 8p23.1 | Mean | cg23007325 | chr8:10924633 | XKR6 | additive | 0.0000000 | 0.0146918 |
| 8p23.1 | Mean | cg18461678 | chr8:10472980 | RP1L1 | additive | 0.0000000 | 0.0091869 |
| 8p23.1 | Mean | cg12618270 | chr8:8667411 | MFHAS1 | additive | 0.0000000 | 0.0090570 |
| 8p23.1 | Mean | cg04880278 | chr8:11597172 | GATA4 | additive | 0.0000000 | -0.0127338 |
| 8p23.1 | Mean | cg24861686 | chr8:11418058 | BLK | additive | 0.0000000 | -0.0095165 |
| 8p23.1 | Mean | cg26552638 | chr8:10875534 | XKR6 | additive | 0.0000000 | 0.0104856 |
| 8p23.1 | Mean | cg03617420 | chr8:10916666 | XKR6 | additive | 0.0000000 | -0.0063183 |
| 8p23.1 | Mean | cg01617280 | chr8:8745938 | MFHAS1 | additive | 0.0000000 | 0.0125593 |
| 8p23.1 | Mean | cg03059247 | chr8:11287657 | C8orf12;FAM167A | additive | 0.0000000 | -0.0059564 |
| 8p23.1 | Mean | cg00718039 | chr8:8681339 | MFHAS1 | additive | 0.0000000 | -0.0075934 |
| 8p23.1 | Mean | cg17329886 | chr8:10513629 | RP1L1 | additive | 0.0000000 | -0.0151366 |
| 8p23.1 | Mean | cg24727203 | chr8:9007933 | PPP1R3B | additive | 0.0000000 | 0.0074513 |
| 8p23.1 | Mean | cg09697033 | chr8:10929599 | XKR6 | additive | 0.0000000 | 0.0116283 |
| 8p23.1 | Mean | cg01048752 | chr8:10001523 | MSRA | additive | 0.0000000 | 0.0099567 |
| 8p23.1 | Mean | cg12637676 | chr8:11587161 | GATA4 | additive | 0.0000000 | 0.0103141 |
| 8p23.1 | Mean | cg17167536 | chr8:10906938 | XKR6 | additive | 0.0000000 | 0.0109941 |
| 8p23.1 | Mean | cg01402994 | chr8:11665969 | FDFT1 | additive | 0.0000000 | -0.0108182 |
| 8p23.1 | Mean | cg19746780 | chr8:11540602 | additive | 0.0000000 | 0.0066767 | |
| 8p23.1 | Mean | cg09768257 | chr8:11628346 | NEIL2 | additive | 0.0000000 | 0.0117662 |
| 8p23.1 | Mean | cg25092989 | chr8:10932494 | XKR6 | additive | 0.0000000 | 0.0065117 |
| 8p23.1 | Mean | cg04335815 | chr8:11417517 | BLK | additive | 0.0000000 | -0.0072381 |
| 8p23.1 | Mean | cg04756296 | chr8:8859877 | ERI1 | additive | 0.0000000 | -0.0095963 |
| 8p23.1 | Mean | cg12641275 | chr8:11411487 | BLK | additive | 0.0000000 | -0.0103945 |
| 8p23.1 | Mean | cg15633056 | chr8:10236882 | MSRA | additive | 0.0000001 | 0.0095738 |
| 8p23.1 | Mean | cg02309752 | chr8:11835607 | recessive | 0.0000001 | 0.0153665 | |
| 8p23.1 | Mean | cg24036517 | chr8:10585394 | SOX7 | additive | 0.0000001 | 0.0084586 |
| 8p23.1 | Mean | cg18217048 | chr8:9742024 | additive | 0.0000001 | -0.0101426 | |
| 8p23.1 | Mean | cg10414350 | chr8:10210282 | MSRA | additive | 0.0000002 | 0.0079841 |
| 8p23.1 | Mean | cg10764196 | chr8:10489270 | RP1L1 | additive | 0.0000002 | 0.0115183 |
| 8p23.1 | Mean | cg24387126 | chr8:11617293 | GATA4 | additive | 0.0000002 | -0.0070235 |
| 8p23.1 | Mean | cg01613189 | chr8:10875246 | XKR6 | additive | 0.0000002 | 0.0067084 |
| 8p23.1 | Mean | cg07593977 | chr8:11735419 | additive | 0.0000003 | -0.0090978 | |
| 8p23.1 | Mean | cg21497594 | chr8:11366745 | BLK | additive | 0.0000003 | 0.0086188 |
| 8p23.1 | Mean | cg27034466 | chr8:11760342 | additive | 0.0000004 | 0.0044595 | |
| 8p23.1 | Mean | cg02525722 | chr8:10404760 | additive | 0.0000004 | 0.0272121 | |
| 8p23.1 | Mean | cg01716419 | chr8:11759663 | additive | 0.0000005 | -0.0051488 | |
| 8p23.1 | Mean | cg10613815 | chr8:11283299 | C8orf12;FAM167A | additive | 0.0000006 | 0.0167254 |
| 8p23.1 | Mean | cg21088119 | chr8:11251471 | C8orf12 | additive | 0.0000006 | -0.0052887 |
| 8p23.1 | Mean | cg16299576 | chr8:10872819 | XKR6 | additive | 0.0000010 | 0.0074867 |
| 8p23.1 | Mean | cg20671920 | chr8:10586678 | SOX7 | additive | 0.0000010 | -0.0086875 |
| 8p23.1 | Mean | cg01535726 | chr8:9911482 | MSRA | additive | 0.0000016 | 0.0069738 |
| 8p23.1 | Mean | cg06182099 | chr8:9789639 | additive | 0.0000024 | -0.0089267 | |
| 8p23.1 | Mean | cg19882315 | chr8:11351846 | BLK | additive | 0.0000029 | 0.0060957 |
| 8p23.1 | Mean | cg20902975 | chr8:11138403 | additive | 0.0000041 | 0.0048105 | |
| 8p23.1 | Mean | cg10805511 | chr8:11843816 | additive | 0.0000043 | 0.0097914 | |
| 8p23.1 | Mean | cg13963446 | chr8:11666017 | FDFT1 | additive | 0.0000058 | -0.0073173 |
| 8p23.1 | Mean | cg26161004 | chr8:11413186 | BLK | additive | 0.0000062 | 0.0054195 |
| 8p23.1 | Mean | cg22974952 | chr8:7212700 | FAM66B | additive | 0.0000063 | -0.0138711 |
| 8p23.1 | Mean | cg27655954 | chr8:10753160 | additive | 0.0000081 | 0.0068565 | |
| 8p23.1 | Mean | cg07755718 | chr8:8639450 | additive | 0.0000089 | 0.0072381 | |
| 8p23.1 | Mean | cg06292304 | chr8:9761905 | MIR124-1;LOC157627 | additive | 0.0000123 | -0.0088454 |
| 8p23.1 | Mean | cg06545268 | chr8:9756974 | additive | 0.0000150 | 0.0110763 | |
| 8p23.1 | Mean | cg18452600 | chr8:9911543 | MSRA | dominant | 0.0000034 | 0.0152856 |
| 8p23.1 | Mean | cg10220992 | chr8:11324327 | FAM167A | additive | 0.0000229 | 0.0079994 |
| 8p23.1 | Mean | cg02621357 | chr8:11296980 | FAM167A | additive | 0.0000260 | 0.0059709 |
| 8p23.1 | Mean | cg19403029 | chr8:10587055 | SOX7 | additive | 0.0000278 | -0.0074851 |
| 8p23.1 | Mean | cg25447652 | chr8:11205754 | TDH | additive | 0.0000300 | -0.0105272 |
| 8p23.1 | Mean | cg26670620 | chr8:12244544 | FAM66A | dominant | 0.0000014 | 0.0327622 |
| 8p23.1 | Mean | cg23565027 | chr8:11021173 | XKR6 | additive | 0.0000406 | 0.0082572 |
| 8p23.1 | Mean | cg01644798 | chr8:11617305 | GATA4 | additive | 0.0000412 | -0.0064120 |
| 8p23.1 | Mean | cg02326058 | chr8:8993102 | additive | 0.0000478 | -0.0082233 | |
| 8p23.1 | Mean | cg21880079 | chr8:8419587 | additive | 0.0000495 | 0.0043253 | |
| 8p23.1 | Mean | cg07890238 | chr8:8182454 | PRAGMIN | recessive | 0.0000093 | 0.0139184 |
| 8p23.1 | Mean | cg01706263 | chr8:10893100 | MIR598;XKR6 | additive | 0.0000535 | 0.0042901 |
| 8p23.1 | Mean | cg14702231 | chr8:11413234 | BLK | additive | 0.0000603 | 0.0066302 |
| 8p23.1 | Mean | cg03024720 | chr8:9765601 | additive | 0.0001131 | -0.0050975 | |
| 8p23.1 | Mean | cg02227026 | chr8:8173791 | recessive | 0.0000268 | 0.0074965 | |
| 8p23.1 | Mean | cg02101571 | chr8:11853878 | DEFB134 | additive | 0.0001419 | 0.0063608 |
| 8p23.1 | Mean | cg22917652 | chr8:10283152 | MSRA | additive | 0.0001516 | 0.0049731 |
| 8p23.1 | Mean | cg26621943 | chr8:10275927 | MSRA | additive | 0.0001524 | -0.0050858 |
| 8p23.1 | Mean | cg04413673 | chr8:10470278 | RP1L1 | additive | 0.0001642 | 0.0069783 |
| 8p23.1 | Mean | cg19996406 | chr8:8318774 | additive | 0.0001786 | -0.0072372 | |
| 8p23.1 | Mean | cg07353006 | chr8:10405104 | dominant | 0.0000243 | 0.0135126 | |
| 8p23.1 | Mean | cg10147394 | chr8:11350297 | BLK | additive | 0.0002023 | 0.0054931 |
| 8p23.1 | Mean | cg26794885 | chr8:12908302 | additive | 0.0002228 | -0.0109642 | |
| 8p23.1 | Mean | cg07229212 | chr8:11056726 | XKR6 | additive | 0.0002275 | -0.0084718 |
| 8p23.1 | Mean | cg03790427 | chr8:10530123 | C8orf74 | additive | 0.0002275 | 0.0052998 |
| 8p23.1 | Mean | cg07756338 | chr8:11882897 | additive | 0.0002343 | 0.0054734 | |
| 8p23.1 | Mean | cg07668586 | chr8:11772215 | additive | 0.0002371 | 0.0050502 | |
| 8p23.1 | Mean | cg04057858 | chr8:10383763 | T-SP1 | additive | 0.0002638 | 0.0032578 |
| 8p23.1 | Mean | cg27515052 | chr8:8513104 | additive | 0.0002744 | -0.0065508 | |
| 8p23.1 | Mean | cg26550646 | chr8:8175407 | PRAGMIN | dominant | 0.0001696 | 0.0057128 |
| 8p23.1 | Mean | cg01619129 | chr8:10697017 | PINX1 | additive | 0.0003417 | -0.0037303 |
| 8p23.1 | Mean | cg08833675 | chr8:10586790 | SOX7 | additive | 0.0003739 | -0.0062212 |
| 8p23.1 | Mean | cg26598540 | chr8:10753147 | additive | 0.0004021 | 0.0095145 | |
| 8p23.1 | Mean | cg24386894 | chr8:8863572 | ERI1 | additive | 0.0004081 | -0.0045402 |
| 8p23.1 | Mean | cg23730558 | chr8:10865623 | XKR6 | additive | 0.0004602 | 0.0052076 |
| 8p23.1 | Mean | cg25377605 | chr8:10513717 | RP1L1 | additive | 0.0004708 | 0.0051469 |
| 8p23.1 | Mean | cg03899229 | chr8:8821258 | dominant | 0.0000115 | -0.0126452 | |
| 8p23.1 | Mean | cg10543574 | chr8:9763159 | additive | 0.0004774 | 0.0058940 | |
| 8p23.1 | Mean | cg27378814 | chr8:12941186 | DLC1 | additive | 0.0004919 | -0.0105938 |
| 8p23.1 | Mean | cg11598005 | chr8:11665962 | FDFT1 | additive | 0.0006336 | -0.0052335 |
| 8p23.1 | Mean | cg03145322 | chr8:10386846 | T-SP1 | additive | 0.0006669 | 0.0067093 |
| 8p23.1 | Mean | cg00115954 | chr8:11536551 | additive | 0.0006717 | -0.0037598 | |
| 8p23.1 | Mean | cg11040268 | chr8:10447472 | additive | 0.0007010 | -0.0055663 | |
| 8p23.1 | Mean | cg07042170 | chr8:8831422 | dominant | 0.0003914 | -0.0123087 | |
| 8p23.1 | Mean | cg01072821 | chr8:10382165 | T-SP1 | recessive | 0.0001000 | -0.0106216 |
| 8p23.1 | Mean | cg15893108 | chr8:7113417 | FAM90A13;FAM90A14 | recessive | 0.0000462 | -0.0176880 |
| 8p23.1 | Mean | cg12810313 | chr8:10192475 | MSRA | additive | 0.0009698 | 0.0050068 |
| 8p23.1 | Mean | cg08711378 | chr8:11471054 | recessive | 0.0001865 | 0.0144154 | |
| 8p23.1 | Mean | cg20633203 | chr8:8239143 | PRAGMIN | additive | 0.0011177 | 0.0044552 |
| 8p23.1 | Mean | cg09300171 | chr8:7434722 | FAM90A7 | additive | 0.0015358 | 0.0037953 |
| 8p23.1 | Mean | cg09817024 | chr8:11471395 | additive | 0.0015621 | 0.0149230 | |
| 8p23.1 | Mean | cg19172575 | chr8:11567721 | GATA4 | additive | 0.0015755 | -0.0030256 |
| 8p23.1 | Mean | cg06940756 | chr8:10927738 | XKR6 | dominant | 0.0011947 | -0.0058283 |
| 8p23.1 | Mean | cg14764956 | chr8:8239338 | PRAGMIN | additive | 0.0019238 | 0.0048690 |
| 8p23.1 | Mean | cg10809491 | chr8:11204833 | TDH | additive | 0.0019357 | 0.0051419 |
| 8p23.1 | Mean | cg20905180 | chr8:11149412 | MTMR9 | dominant | 0.0003914 | 0.0143081 |
| 8p23.1 | Mean | cg02457461 | chr8:9913680 | MSRA | additive | 0.0020415 | 0.0061514 |
| 8p23.1 | Mean | cg08596486 | chr8:12938311 | additive | 0.0020849 | -0.0054848 | |
| 8p23.1 | Mean | cg24899626 | chr8:10512724 | RP1L1 | additive | 0.0022892 | 0.0047481 |
| 8p23.1 | Mean | cg24338833 | chr8:10592227 | additive | 0.0023027 | 0.0044411 | |
| 8p23.1 | Mean | cg20213479 | chr8:10460029 | additive | 0.0023204 | 0.0036499 | |
| 8p23.1 | Mean | cg12996100 | chr8:11470690 | additive | 0.0023394 | 0.0063445 | |
| 8p23.1 | Mean | cg02109073 | chr8:8176460 | PRAGMIN | dominant | 0.0005604 | 0.0116807 |
| 8p23.1 | Mean | cg16847396 | chr8:10489236 | RP1L1 | recessive | 0.0007180 | 0.0086628 |
| 8p23.1 | Mean | cg10419849 | chr8:9537322 | TNKS | additive | 0.0028300 | 0.0038786 |
| 8p23.1 | Mean | cg10823658 | chr8:10919403 | XKR6 | dominant | 0.0025652 | 0.0059496 |
| 8p23.1 | Mean | cg24415728 | chr8:11471816 | additive | 0.0030840 | 0.0080598 | |
| 8p23.1 | Mean | cg10585806 | chr8:9987847 | MSRA | additive | 0.0030908 | 0.0049167 |
| 8p23.1 | Mean | cg01359236 | chr8:11763828 | recessive | 0.0007056 | 0.0081301 | |
| 8p23.1 | Mean | cg05852732 | chr8:11832565 | DEFB136 | additive | 0.0035550 | 0.0053279 |
| 8p23.1 | Mean | cg27030482 | chr8:11539320 | additive | 0.0037144 | 0.0060514 | |
| 8p23.1 | Mean | cg13519851 | chr8:10916560 | XKR6 | recessive | 0.0000434 | -0.0126974 |
| 8p23.1 | Mean | cg07301044 | chr8:9765583 | additive | 0.0040475 | -0.0057308 | |
| 8p23.1 | Mean | cg26788142 | chr8:11747049 | additive | 0.0045068 | -0.0031013 | |
| 8p23.1 | Mean | cg09052083 | chr8:10873619 | XKR6 | additive | 0.0046082 | -0.0050120 |
| 8p23.1 | Mean | cg25083091 | chr8:10646690 | PINX1 | dominant | 0.0045484 | 0.0063943 |
| 8p23.1 | Mean | cg02601489 | chr8:11203954 | TDH | additive | 0.0050200 | 0.0090877 |
| 8p23.1 | Mean | cg09974041 | chr8:10273890 | MSRA | additive | 0.0050489 | -0.0030941 |
| 8p23.1 | Mean | cg11320910 | chr8:11538786 | additive | 0.0052387 | 0.0020605 | |
| 8p23.1 | Mean | cg12981288 | chr8:11183844 | MTMR9 | additive | 0.0055238 | 0.0032818 |
| 8p23.1 | Mean | cg18127003 | chr8:11614472 | GATA4 | additive | 0.0055238 | -0.0035406 |
| 8p23.1 | Mean | cg07556789 | chr8:11538570 | additive | 0.0055386 | 0.0021348 | |
| 8p23.1 | Mean | cg17526103 | chr8:9765691 | additive | 0.0055820 | -0.0065900 | |
| 8p23.1 | Mean | cg12807628 | chr8:11838843 | DEFB135 | additive | 0.0055820 | 0.0042255 |
| 8p23.1 | Mean | cg16284953 | chr8:11471571 | additive | 0.0058740 | 0.0071390 | |
| 8p23.1 | Mean | cg04879378 | chr8:10929210 | XKR6 | additive | 0.0069301 | 0.0047191 |
| 8p23.1 | Mean | cg24574147 | chr8:10918572 | XKR6 | additive | 0.0070411 | 0.0039270 |
| 8p23.1 | Mean | cg01131038 | chr8:10592118 | dominant | 0.0054092 | 0.0090784 | |
| 8p23.1 | Mean | cg06952801 | chr8:10460235 | additive | 0.0074275 | 0.0060125 | |
| 8p23.1 | Mean | cg06266132 | chr8:11853121 | DEFB134 | additive | 0.0075776 | 0.0054523 |
| 8p23.1 | Mean | cg05759166 | chr8:10452896 | additive | 0.0085096 | 0.0049364 | |
| 8p23.1 | Mean | cg16782885 | chr8:11541421 | additive | 0.0085233 | 0.0068567 | |
| 8p23.1 | Mean | cg02898412 | chr8:11623524 | additive | 0.0091606 | 0.0050782 | |
| 8p23.1 | Mean | cg25519723 | chr8:8402366 | additive | 0.0094668 | 0.0029393 | |
| 8p23.1 | Mean | cg20819482 | chr8:9472057 | TNKS | additive | 0.0095947 | -0.0048889 |
| 8p23.1 | Mean | cg11374933 | chr8:9766172 | additive | 0.0101221 | 0.0045496 | |
| 8p23.1 | Mean | cg04218812 | chr8:9763263 | additive | 0.0104174 | 0.0042666 | |
| 8p23.1 | Mean | cg25455865 | chr8:8960015 | recessive | 0.0104721 | 0.0071077 | |
| 8p23.1 | Mean | cg07291889 | chr8:11471712 | additive | 0.0111515 | 0.0049492 | |
| 8p23.1 | Mean | cg07356412 | chr8:11044280 | XKR6 | additive | 0.0115780 | 0.0030463 |
| 8p23.1 | Mean | cg01489256 | chr8:11204017 | TDH | additive | 0.0117034 | -0.0103298 |
| 8p23.1 | Mean | cg13283153 | chr8:9756828 | additive | 0.0117767 | 0.0045982 | |
| 8p23.1 | Mean | cg23158754 | chr8:9766135 | additive | 0.0118898 | -0.0058709 | |
| 8p23.1 | Mean | cg06869039 | chr8:12838022 | C8orf79 | additive | 0.0133644 | -0.0055239 |
| 8p23.1 | Mean | cg04291970 | chr8:11226339 | C8orf12 | additive | 0.0146165 | 0.0039770 |
| 8p23.1 | Mean | cg26339990 | chr8:12878608 | C8orf79 | additive | 0.0148870 | -0.0047243 |
| 8p23.1 | Mean | cg17155499 | chr8:11644644 | NEIL2 | dominant | 0.0016184 | 0.0071299 |
| 8p23.1 | Mean | cg09031473 | chr8:10593133 | dominant | 0.0120959 | 0.0051498 | |
| 8p23.1 | Mean | cg09500200 | chr8:9763033 | recessive | 0.0110124 | -0.0074537 | |
| 8p23.1 | Mean | cg08447380 | chr8:8185703 | PRAGMIN | additive | 0.0158063 | 0.0024195 |
| 8p23.1 | Mean | cg08196601 | chr8:12869553 | C8orf79 | recessive | 0.0044940 | -0.0092654 |
| 8p23.1 | Mean | cg00870242 | chr8:10530148 | C8orf74 | additive | 0.0173984 | 0.0027906 |
| 8p23.1 | Mean | cg17981470 | chr8:10470999 | RP1L1 | additive | 0.0178878 | 0.0040340 |
| 8p23.1 | Mean | cg07935657 | chr8:10622805 | additive | 0.0182818 | 0.0105775 | |
| 8p23.1 | Mean | cg09460231 | chr8:10736649 | additive | 0.0184161 | 0.0053629 | |
| 8p23.1 | Mean | cg27108504 | chr8:10123853 | MSRA | additive | 0.0188582 | -0.0032791 |
| 8p23.1 | Mean | cg11824826 | chr8:9953022 | MSRA | recessive | 0.0059706 | 0.0057774 |
| 8p23.1 | Mean | cg21919729 | chr8:11719367 | CTSB | dominant | 0.0186866 | 0.0083721 |
| 8p23.1 | Mean | cg02310165 | chr8:10892734 | XKR6;MIR598 | additive | 0.0208055 | 0.0035155 |
| 8p23.1 | Mean | cg03192020 | chr8:11204681 | TDH | dominant | 0.0161481 | 0.0055014 |
| 8p23.1 | Mean | cg17802537 | chr8:8857094 | additive | 0.0212431 | -0.0038001 | |
| 8p23.1 | Mean | cg26020513 | chr8:11568356 | GATA4 | additive | 0.0215001 | 0.0071033 |
| 8p23.1 | Mean | cg24520755 | chr8:9996632 | MSRA | additive | 0.0215100 | -0.0036860 |
| 8p23.1 | Mean | cg05362548 | chr8:11205166 | TDH | additive | 0.0215100 | 0.0031058 |
| 8p23.1 | Mean | cg20781335 | chr8:10466983 | RP1L1 | additive | 0.0215100 | 0.0040070 |
| 8p23.1 | Mean | cg08911368 | chr8:11471085 | additive | 0.0215100 | 0.0091888 | |
| 8p23.1 | Mean | cg13440795 | chr8:10210267 | MSRA | dominant | 0.0016285 | 0.0070063 |
| 8p23.1 | Mean | cg21535000 | chr8:9760877 | LOC157627 | dominant | 0.0090629 | 0.0053863 |
| 8p23.1 | Mean | cg07068655 | chr8:12633029 | LOC340357 | dominant | 0.0094670 | -0.0037314 |
| 8p23.1 | Mean | cg15906055 | chr8:11195919 | TDH | dominant | 0.0102963 | -0.0047886 |
| 8p23.1 | Mean | cg04657224 | chr8:11059038 | XKR6 | dominant | 0.0108584 | 0.0035216 |
| 8p23.1 | Mean | cg25191598 | chr8:12809941 | C8orf79 | dominant | 0.0139446 | 0.0063202 |
| 8p23.1 | Mean | cg04345694 | chr8:8439596 | dominant | 0.0209244 | 0.0046635 | |
| 8p23.1 | Mean | cg18420643 | chr8:10590503 | recessive | 0.0017669 | 0.0071280 | |
| 8p23.1 | Mean | cg13434842 | chr8:11567896 | GATA4 | recessive | 0.0045562 | -0.0082657 |
| 8p23.1 | Mean | cg02935780 | chr8:12788931 | recessive | 0.0098587 | -0.0104883 | |
| 8p23.1 | Mean | cg23282442 | chr8:11225832 | C8orf12;TDH | recessive | 0.0117378 | 0.0072181 |
| 8p23.1 | Mean | cg27044841 | chr8:8580960 | recessive | 0.0173661 | -0.0124387 | |
| 8p23.1 | Mean | cg22883125 | chr8:11540758 | recessive | 0.0189570 | 0.0098727 | |
| 8p23.1 | Mean | cg04015433 | chr8:8820844 | recessive | 0.0195630 | 0.0111140 | |
| 8p23.1 | Mean | cg27100760 | chr8:10708248 | recessive | 0.0209381 | -0.0083211 |
Figure 12: Enrichment analysis results for mean differentially methylated (MDM) genes in inversion 8p23.1 using GO database
Inversion 16p11.2
The CpG sites that appear in Table 7 are DMD according to the 16p11.2 region status. Moreover, the enrichment of the genes that contain these CpG sites is presented in Figure 13.
| Inversion | Type_analysis | CpG | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|
| 16p11.2 | Mean | cg09046979 | chr16:28333134 | SBK1 | additive | 0.0000000 | -0.0590529 |
| 16p11.2 | Mean | cg04270652 | chr16:28608894 | SULT1A2 | additive | 0.0000000 | -0.0301901 |
| 16p11.2 | Mean | cg27413008 | chr16:28519597 | IL27 | additive | 0.0000000 | -0.0345394 |
| 16p11.2 | Mean | cg26624097 | chr16:28620651 | SULT1A1 | additive | 0.0000000 | 0.0426758 |
| 16p11.2 | Mean | cg01542023 | chr16:28550637 | NUPR1 | additive | 0.0000000 | -0.0218598 |
| 16p11.2 | Mean | cg02896250 | chr16:28305533 | SBK1 | additive | 0.0000000 | -0.0147799 |
| 16p11.2 | Mean | cg17122311 | chr16:28517278 | IL27 | additive | 0.0000000 | -0.0115008 |
| 16p11.2 | Mean | cg05683445 | chr16:28303182 | SBK1 | additive | 0.0000000 | 0.0138940 |
| 16p11.2 | Mean | cg00348858 | chr16:28858442 | TUFM | additive | 0.0000000 | -0.0161799 |
| 16p11.2 | Mean | cg03300649 | chr16:28504949 | APOB48R;CLN3 | additive | 0.0000000 | -0.0112055 |
| 16p11.2 | Mean | cg01378222 | chr16:28622494 | SULT1A1 | additive | 0.0000000 | 0.0201353 |
| 16p11.2 | Mean | cg00201760 | chr16:28518385 | IL27 | additive | 0.0000000 | -0.0066276 |
| 16p11.2 | Mean | cg26792089 | chr16:28518200 | IL27 | additive | 0.0000000 | -0.0086291 |
| 16p11.2 | Mean | cg01621080 | chr16:28608125 | SULT1A2 | additive | 0.0000000 | -0.0191912 |
| 16p11.2 | Mean | cg09754948 | chr16:28834200 | ATXN2L | additive | 0.0000000 | 0.0207868 |
| 16p11.2 | Mean | cg08761264 | chr16:28874980 | SH2B1 | additive | 0.0000000 | -0.0146328 |
| 16p11.2 | Mean | cg26603685 | chr16:28620355 | SULT1A1 | additive | 0.0000000 | 0.0141158 |
| 16p11.2 | Mean | cg02195680 | chr16:28519566 | IL27 | additive | 0.0000000 | -0.0083101 |
| 16p11.2 | Mean | cg06726893 | chr16:28870846 | additive | 0.0000000 | -0.0128628 | |
| 16p11.2 | Mean | cg06288570 | chr16:28550567 | NUPR1 | additive | 0.0000000 | 0.0075608 |
| 16p11.2 | Mean | cg08180572 | chr16:28985143 | SPNS1 | additive | 0.0000000 | -0.0213145 |
| 16p11.2 | Mean | cg27016020 | chr16:28303432 | SBK1 | additive | 0.0000000 | 0.0105083 |
| 16p11.2 | Mean | cg10436792 | chr16:28889110 | ATP2A1 | additive | 0.0000000 | -0.0134999 |
| 16p11.2 | Mean | cg07884168 | chr16:28874307 | SH2B1 | additive | 0.0000018 | -0.0189530 |
| 16p11.2 | Mean | cg04413090 | chr16:28302913 | SBK1 | additive | 0.0000018 | 0.0083194 |
| 16p11.2 | Mean | cg05590982 | chr16:28550171 | NUPR1 | additive | 0.0000039 | 0.0083566 |
| 16p11.2 | Mean | cg00272903 | chr16:28300253 | additive | 0.0000089 | 0.0096998 | |
| 16p11.2 | Mean | cg00536289 | chr16:28834130 | ATXN2L | dominant | 0.0000037 | -0.0064095 |
| 16p11.2 | Mean | cg04244056 | chr16:28835698 | ATXN2L | additive | 0.0000218 | 0.0063856 |
| 16p11.2 | Mean | cg26489497 | chr16:28512017 | IL27 | additive | 0.0000324 | 0.0042995 |
| 16p11.2 | Mean | cg00489954 | chr16:28855387 | TUFM | dominant | 0.0000451 | 0.0061871 |
| 16p11.2 | Mean | cg27473355 | chr16:28915234 | ATP2A1 | additive | 0.0000834 | 0.0040903 |
| 16p11.2 | Mean | cg08213689 | chr16:28893874 | ATP2A1 | additive | 0.0001154 | 0.0076508 |
| 16p11.2 | Mean | cg01161644 | chr16:28270238 | additive | 0.0001154 | -0.0082059 | |
| 16p11.2 | Mean | cg25341726 | chr16:28518331 | IL27 | additive | 0.0001685 | -0.0052976 |
| 16p11.2 | Mean | cg26663590 | chr16:28959310 | additive | 0.0002295 | 0.0058851 | |
| 16p11.2 | Mean | cg00204512 | chr16:28754710 | dominant | 0.0000326 | -0.0060013 | |
| 16p11.2 | Mean | cg08726667 | chr16:28573379 | CCDC101 | additive | 0.0004551 | 0.0053023 |
| 16p11.2 | Mean | cg02329193 | chr16:29196472 | additive | 0.0011103 | -0.0044675 | |
| 16p11.2 | Mean | cg04609801 | chr16:28609176 | SULT1A2 | additive | 0.0024163 | -0.0061258 |
| 16p11.2 | Mean | cg26872100 | chr16:28270754 | additive | 0.0067904 | -0.0050429 | |
| 16p11.2 | Mean | cg26701545 | chr16:28331026 | SBK1 | dominant | 0.0073350 | -0.0071532 |
| 16p11.2 | Mean | cg16576597 | chr16:28551801 | NUPR1 | additive | 0.0085387 | 0.0043544 |
| 16p11.2 | Mean | cg06723057 | chr16:28549923 | NUPR1 | additive | 0.0112408 | 0.0025291 |
| 16p11.2 | Mean | cg06897606 | chr16:28270673 | additive | 0.0122980 | -0.0059785 | |
| 16p11.2 | Mean | cg02358434 | chr16:28995271 | SPNS1;LAT | dominant | 0.0126779 | 0.0044088 |
| 16p11.2 | Mean | cg04761177 | chr16:28898644 | ATP2A1 | dominant | 0.0149695 | -0.0050702 |
| 16p11.2 | Mean | cg05280508 | chr16:28486629 | dominant | 0.0081569 | -0.0067688 | |
| 16p11.2 | Mean | cg11094938 | chr16:28888844 | ATP2A1 | additive | 0.0213980 | -0.0026259 |
| 16p11.2 | Mean | cg12743398 | chr16:28609531 | SULT1A2 | dominant | 0.0022667 | 0.0187413 |
Figure 13: Enrichment analysis results for mean differentially methylated (MDM) genes in inversion 16p11.2
A) Results for the enrichment using DisGeNET database; B) Enrichment results using GO.
Inversion 17q21.31
Table 8 displays the CpG sites DMD depending on the inversion 17q21.31 genotype. Their respective genes have been used for an enrichment analysis which results are shown in Figure 14.
| Inversion | Type_analysis | CpG | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|
| 17q21.31 | Mean | cg05159804 | chr17:44343776 | additive | 0.0000000 | -0.1129002 | |
| 17q21.31 | Mean | cg22968622 | chr17:43663579 | dominant | 0.0000000 | 0.4881827 | |
| 17q21.31 | Mean | cg12609785 | chr17:43660871 | additive | 0.0000000 | 0.2598851 | |
| 17q21.31 | Mean | cg19832721 | chr17:44249866 | KIAA1267 | additive | 0.0000000 | 0.1195135 |
| 17q21.31 | Mean | cg08113562 | chr17:43508428 | SH3D20 | additive | 0.0000000 | 0.1300643 |
| 17q21.31 | Mean | cg09764761 | chr17:44105544 | MAPT | additive | 0.0000000 | -0.0517372 |
| 17q21.31 | Mean | cg07368061 | chr17:44090862 | MAPT | additive | 0.0000000 | -0.0466625 |
| 17q21.31 | Mean | cg01341218 | chr17:43662625 | additive | 0.0000000 | 0.0410505 | |
| 17q21.31 | Mean | cg01882395 | chr17:43717810 | C17orf69 | additive | 0.0000000 | 0.0346404 |
| 17q21.31 | Mean | cg03954353 | chr17:43715162 | C17orf69;MGC57346 | additive | 0.0000000 | 0.0315196 |
| 17q21.31 | Mean | cg00891649 | chr17:43972573 | MAPT;LOC100130148;LOC100128977 | additive | 0.0000000 | -0.0343202 |
| 17q21.31 | Mean | cg14374015 | chr17:44249569 | KIAA1267 | additive | 0.0000000 | 0.0338557 |
| 17q21.31 | Mean | cg22433210 | chr17:43662623 | additive | 0.0000000 | 0.0315742 | |
| 17q21.31 | Mean | cg23659289 | chr17:43472725 | ARHGAP27 | additive | 0.0000000 | 0.0164382 |
| 17q21.31 | Mean | cg05301556 | chr17:43971177 | MAPT;LOC100128977 | additive | 0.0000000 | -0.0270672 |
| 17q21.31 | Mean | cg27503360 | chr17:43890749 | CRHR1 | additive | 0.0000000 | -0.0162679 |
| 17q21.31 | Mean | cg21214508 | chr17:44248233 | KIAA1267 | additive | 0.0000000 | -0.0322238 |
| 17q21.31 | Mean | cg05772917 | chr17:44027251 | MAPT | additive | 0.0000000 | 0.0171359 |
| 17q21.31 | Mean | cg04491389 | chr17:44214771 | KIAA1267 | additive | 0.0000000 | -0.0305095 |
| 17q21.31 | Mean | cg13732302 | chr17:44222207 | KIAA1267 | additive | 0.0000000 | -0.0279081 |
| 17q21.31 | Mean | cg08670715 | chr17:44341754 | dominant | 0.0000000 | 0.0370365 | |
| 17q21.31 | Mean | cg23616531 | chr17:44269258 | additive | 0.0000000 | -0.0339657 | |
| 17q21.31 | Mean | cg01934064 | chr17:44064242 | MAPT | additive | 0.0000000 | 0.0234691 |
| 17q21.31 | Mean | cg07368127 | chr17:44230994 | KIAA1267 | additive | 0.0000000 | 0.0318063 |
| 17q21.31 | Mean | cg05186793 | chr17:44235520 | KIAA1267 | additive | 0.0000000 | 0.0344788 |
| 17q21.31 | Mean | cg23952828 | chr17:44246087 | KIAA1267 | additive | 0.0000000 | 0.0154349 |
| 17q21.31 | Mean | cg18410271 | chr17:43472435 | ARHGAP27 | additive | 0.0000000 | 0.0074472 |
| 17q21.31 | Mean | cg26855231 | chr17:44249543 | KIAA1267 | additive | 0.0000000 | 0.0226924 |
| 17q21.31 | Mean | cg07067577 | chr17:43506829 | SH3D20 | additive | 0.0000000 | -0.0113738 |
| 17q21.31 | Mean | cg24063856 | chr17:43863303 | CRHR1 | additive | 0.0000000 | -0.0260940 |
| 17q21.31 | Mean | cg19943578 | chr17:43483527 | ARHGAP27 | additive | 0.0000000 | -0.0113516 |
| 17q21.31 | Mean | cg00480298 | chr17:44068857 | MAPT | additive | 0.0000000 | 0.0230431 |
| 17q21.31 | Mean | cg02301815 | chr17:44249491 | KIAA1267 | additive | 0.0000000 | -0.0204581 |
| 17q21.31 | Mean | cg12798194 | chr17:43462791 | additive | 0.0000000 | 0.0187522 | |
| 17q21.31 | Mean | cg24203758 | chr17:43507018 | SH3D20 | additive | 0.0000000 | -0.0229969 |
| 17q21.31 | Mean | cg13947929 | chr17:43863356 | CRHR1 | additive | 0.0000000 | -0.0116069 |
| 17q21.31 | Mean | cg22128613 | chr17:44061117 | MAPT | additive | 0.0000000 | 0.0170594 |
| 17q21.31 | Mean | cg12604352 | chr17:44073915 | MAPT | additive | 0.0000000 | -0.0229072 |
| 17q21.31 | Mean | cg10955972 | chr17:43976002 | MAPT;LOC100130148 | additive | 0.0000000 | 0.0103646 |
| 17q21.31 | Mean | cg17554502 | chr17:44271559 | additive | 0.0000000 | 0.0168114 | |
| 17q21.31 | Mean | cg10224600 | chr17:43975063 | MAPT;LOC100130148 | additive | 0.0000000 | 0.0197249 |
| 17q21.31 | Mean | cg26250449 | chr17:44195907 | KIAA1267 | additive | 0.0000000 | -0.0200634 |
| 17q21.31 | Mean | cg16642545 | chr17:43878769 | CRHR1 | additive | 0.0000000 | -0.0120099 |
| 17q21.31 | Mean | cg07584200 | chr17:44185029 | KIAA1267 | additive | 0.0000000 | 0.0142890 |
| 17q21.31 | Mean | cg27551605 | chr17:43862910 | CRHR1 | additive | 0.0000000 | -0.0116885 |
| 17q21.31 | Mean | cg06491244 | chr17:44851046 | WNT3 | additive | 0.0000000 | 0.0056960 |
| 17q21.31 | Mean | cg00715050 | chr17:43472920 | ARHGAP27 | additive | 0.0000000 | 0.0079899 |
| 17q21.31 | Mean | cg14260695 | chr17:43506184 | additive | 0.0000000 | -0.0132760 | |
| 17q21.31 | Mean | cg08358943 | chr17:44889584 | WNT3 | additive | 0.0000000 | 0.0114873 |
| 17q21.31 | Mean | cg19872068 | chr17:44250734 | KIAA1267 | additive | 0.0000000 | -0.0097687 |
| 17q21.31 | Mean | cg05251861 | chr17:43503394 | ARHGAP27 | additive | 0.0000000 | -0.0154974 |
| 17q21.31 | Mean | cg18119429 | chr17:44270215 | additive | 0.0000000 | 0.0130878 | |
| 17q21.31 | Mean | cg01640727 | chr17:44029468 | MAPT | dominant | 0.0000000 | -0.0186422 |
| 17q21.31 | Mean | cg00025823 | chr17:43909151 | CRHR1 | additive | 0.0000000 | 0.0108103 |
| 17q21.31 | Mean | cg02665463 | chr17:44657154 | ARL17A | additive | 0.0000001 | 0.0515584 |
| 17q21.31 | Mean | cg13465858 | chr17:44204908 | KIAA1267 | additive | 0.0000001 | -0.0151230 |
| 17q21.31 | Mean | cg00677574 | chr17:43221327 | ACBD4 | additive | 0.0000001 | -0.0285180 |
| 17q21.31 | Mean | cg06100756 | chr17:43221575 | dominant | 0.0000002 | -0.0272045 | |
| 17q21.31 | Mean | cg00348467 | chr17:43222121 | dominant | 0.0000001 | -0.0153352 | |
| 17q21.31 | Mean | cg07778819 | chr17:43862927 | CRHR1 | dominant | 0.0000001 | -0.0129000 |
| 17q21.31 | Mean | cg00625783 | chr17:43222106 | additive | 0.0000012 | -0.0098780 | |
| 17q21.31 | Mean | cg17372941 | chr17:43222115 | dominant | 0.0000010 | -0.0100327 | |
| 17q21.31 | Mean | cg17178468 | chr17:43049442 | additive | 0.0000045 | 0.0049710 | |
| 17q21.31 | Mean | cg27395066 | chr17:43221220 | ACBD4 | additive | 0.0000045 | -0.0288361 |
| 17q21.31 | Mean | cg02932314 | chr17:42733698 | C17orf104 | additive | 0.0000070 | -0.0145782 |
| 17q21.31 | Mean | cg15072306 | chr17:43922875 | LOC100128977;IMP5 | additive | 0.0000080 | -0.0064886 |
| 17q21.31 | Mean | cg15156975 | chr17:43449055 | additive | 0.0000129 | -0.0120818 | |
| 17q21.31 | Mean | cg06471905 | chr17:42835688 | ADAM11 | additive | 0.0000151 | 0.0037251 |
| 17q21.31 | Mean | cg12127472 | chr17:42733724 | C17orf104 | additive | 0.0000231 | -0.0172817 |
| 17q21.31 | Mean | cg06649191 | chr17:42908211 | GJC1 | additive | 0.0000372 | 0.0095219 |
| 17q21.31 | Mean | cg00022871 | chr17:43884358 | CRHR1 | additive | 0.0001391 | -0.0049349 |
| 17q21.31 | Mean | cg16573346 | chr17:44020278 | MAPT | additive | 0.0001450 | 0.0094528 |
| 17q21.31 | Mean | cg10701640 | chr17:43249399 | additive | 0.0002350 | -0.0175842 | |
| 17q21.31 | Mean | cg04976685 | chr17:43449285 | additive | 0.0003154 | -0.0100207 | |
| 17q21.31 | Mean | cg15639951 | chr17:43367609 | MAP3K14 | additive | 0.0003257 | -0.0042282 |
| 17q21.31 | Mean | cg06729642 | chr17:43324793 | LOC100133991 | dominant | 0.0002123 | -0.0095029 |
| 17q21.31 | Mean | cg08929103 | chr17:43860355 | CRHR1 | additive | 0.0003648 | -0.0046606 |
| 17q21.31 | Mean | cg09581049 | chr17:42998320 | additive | 0.0003739 | 0.0052022 | |
| 17q21.31 | Mean | cg13215995 | chr17:43222258 | additive | 0.0005163 | -0.0049477 | |
| 17q21.31 | Mean | cg25105522 | chr17:43355089 | MAP3K14 | additive | 0.0005636 | 0.0122137 |
| 17q21.31 | Mean | cg24180402 | chr17:43221464 | ACBD4 | additive | 0.0005851 | -0.0110929 |
| 17q21.31 | Mean | cg08496953 | chr17:42733527 | C17orf104 | additive | 0.0007656 | -0.0160496 |
| 17q21.31 | Mean | cg13550419 | chr17:44898510 | additive | 0.0009796 | -0.0049300 | |
| 17q21.31 | Mean | cg04382470 | chr17:43974975 | MAPT;LOC100130148 | additive | 0.0011534 | 0.0072692 |
| 17q21.31 | Mean | cg07993743 | chr17:44928288 | WNT9B | additive | 0.0012075 | -0.0087875 |
| 17q21.31 | Mean | cg04992638 | chr17:43339328 | C17orf46;LOC100133991 | additive | 0.0012153 | 0.0040613 |
| 17q21.31 | Mean | cg11969213 | chr17:43324322 | LOC100133991;FMNL1 | additive | 0.0015940 | -0.0064094 |
| 17q21.31 | Mean | cg19407385 | chr17:43099144 | dominant | 0.0010953 | 0.0261416 | |
| 17q21.31 | Mean | cg24349819 | chr17:43476547 | ARHGAP27 | dominant | 0.0011522 | 0.0047931 |
| 17q21.31 | Mean | cg03785666 | chr17:43324416 | LOC100133991;FMNL1 | additive | 0.0017830 | -0.0060942 |
| 17q21.31 | Mean | cg03209459 | chr17:44604660 | ARL17A;LRRC37A2 | additive | 0.0019379 | -0.0108676 |
| 17q21.31 | Mean | cg09250749 | chr17:44271316 | additive | 0.0021367 | 0.0074298 | |
| 17q21.31 | Mean | cg20840174 | chr17:44087784 | MAPT | additive | 0.0023942 | -0.0037086 |
| 17q21.31 | Mean | cg15690475 | chr17:44101453 | MAPT | dominant | 0.0006506 | -0.0058092 |
| 17q21.31 | Mean | cg24394631 | chr17:43863000 | CRHR1 | additive | 0.0029465 | -0.0080932 |
| 17q21.31 | Mean | cg23907852 | chr17:43922244 | LOC100128977;IMP5 | additive | 0.0032991 | 0.0028090 |
| 17q21.31 | Mean | cg10598582 | chr17:43093761 | additive | 0.0047092 | 0.0051398 | |
| 17q21.31 | Mean | cg12286573 | chr17:42734503 | C17orf104 | additive | 0.0047092 | 0.0092711 |
| 17q21.31 | Mean | cg24677220 | chr17:44075684 | MAPT;STH | dominant | 0.0014669 | 0.0067886 |
| 17q21.31 | Mean | cg27457921 | chr17:43976811 | MAPT | dominant | 0.0020022 | 0.0073739 |
| 17q21.31 | Mean | cg21095561 | chr17:42733994 | C17orf104 | dominant | 0.0047407 | -0.0100535 |
| 17q21.31 | Mean | cg12633764 | chr17:43978756 | MAPT | additive | 0.0058811 | 0.0034843 |
| 17q21.31 | Mean | cg10256219 | chr17:44270511 | additive | 0.0069141 | 0.0074597 | |
| 17q21.31 | Mean | cg01440864 | chr17:44892087 | WNT3 | additive | 0.0086836 | 0.0058238 |
| 17q21.31 | Mean | cg19539667 | chr17:43339831 | LOC100133991;C17orf46 | additive | 0.0090486 | -0.0036384 |
| 17q21.31 | Mean | cg03706109 | chr17:43090472 | additive | 0.0092657 | 0.0048153 | |
| 17q21.31 | Mean | cg16734549 | chr17:43488551 | ARHGAP27 | dominant | 0.0044139 | 0.0044700 |
| 17q21.31 | Mean | cg19156875 | chr17:43974446 | MAPT;LOC100130148 | recessive | 0.0107245 | 0.0168792 |
| 17q21.31 | Mean | cg03723148 | chr17:43921863 | LOC100128977;IMP5 | recessive | 0.0029048 | -0.0082081 |
| 17q21.31 | Mean | cg14633020 | chr17:43194301 | PLCD3 | additive | 0.0120489 | 0.0049921 |
| 17q21.31 | Mean | cg25560772 | chr17:45057470 | RPRML | dominant | 0.0071130 | -0.0116417 |
| 17q21.31 | Mean | cg20769177 | chr17:44928516 | WNT9B | additive | 0.0127040 | -0.0178243 |
| 17q21.31 | Mean | cg16772514 | chr17:43046872 | C1QL1 | additive | 0.0135717 | 0.0020695 |
| 17q21.31 | Mean | cg26226202 | chr17:44928552 | WNT9B | additive | 0.0140419 | -0.0098593 |
| 17q21.31 | Mean | cg17881353 | chr17:44928210 | WNT9B | dominant | 0.0108268 | -0.0157611 |
| 17q21.31 | Mean | cg18050844 | chr17:44909987 | additive | 0.0208820 | 0.0056215 | |
| 17q21.31 | Mean | cg12393668 | chr17:42768503 | CCDC43 | dominant | 0.0212097 | -0.0066238 |
| 17q21.31 | Mean | cg19563671 | chr17:43224158 | HEXIM1 | dominant | 0.0042189 | 0.0229999 |
| 17q21.31 | Mean | cg24042242 | chr17:43044660 | C1QL1 | dominant | 0.0071874 | -0.0128387 |
| 17q21.31 | Mean | cg08301612 | chr17:43228571 | HEXIM1 | dominant | 0.0130497 | -0.0076557 |
| 17q21.31 | Mean | cg14630905 | chr17:44928992 | WNT9B | recessive | 0.0074608 | 0.0159778 |
| 17q21.31 | Mean | cg04102519 | chr17:44843875 | WNT3 | recessive | 0.0122555 | 0.0152973 |
| 17q21.31 | Mean | cg12297030 | chr17:43662878 | recessive | 0.0188742 | 0.0115852 |
Figure 14: Enrichment analysis results for mean differentially methylated (MDM) genes in inversion 17q21.31
A) Enrichment results using KEGG; B) Results for the enrichment using GO database.
Table 9 shows the only metabolite differentially concentrated according to the inversion 8p23.1 genotype.
| Metabolome | Inversion | Type_analysis | Metabolite | model | adj.P.Val | DiffLevene_logFC |
|---|---|---|---|---|---|---|
| Urine | 8p23.1 | Mean | Sucrose | additive | 0.0199054 | 0.2819581 |
| Urine | 8p23.1 | Mean | Sucrose | dominant | 0.0131570 | 0.4482716 |
The results of the differential analysis according to the genotype*exposure are displayed in Table 10 and Figure 15 for inverison 8p23.1, Table 11 and Figure 17 for inversion 16p11.2, and Table 12 and Figures 18 and 19 for inversion 17q21.31. The only enrichment analysis that has revealed results is the one that has used MDE genes for inversion 8p23.1 (Figure 16).
Inversion 8p23.1
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | Transcript | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|---|---|
| h_ln_cat_preg_None | Traffic noise (night) | Noise | 8p23.1 | Mean | TC08000963.hg.1 | chr8:10713595-10716946 | AK094525 | 0.0457837 | 0.0739552 |
| h_ln_cat_preg_None | Traffic noise (night) | Noise | 8p23.1 | Mean | TC08000949.hg.1 | chr8:9144982-9145088 | RNU6-1151P;U6 | 0.0457837 | -0.1240038 |
| h_pressure_t1_None | Pressure (t1) | Meteorological | 8p23.1 | Mean | TC08000919.hg.1 | chr8:7272382-7274385 | DEFB4B | 0.0318741 | 0.0035486 |
| hs_bpa_madj_Log2 | BPA | Phenols | 8p23.1 | Mean | TC08000077.hg.1 | chr8:10383056-10411676 | PRSS55 | 0.0315433 | 0.0171205 |
| hs_pbde47_madj_Log2 | PBDE 47 | PBDEs | 8p23.1 | Mean | TC08002212.hg.1 | chr8:9757531-9762876 | LINC00599 | 0.0297172 | -0.0132029 |
Figure 15: Plot representations for the mean differentially expressed genes when inversion 8p23.1 interacts with exposome
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 16: Enrichment analysis for mean differentially expressed (MDE) genes using genotype-environment interaction for inversion 8p23.1
A) Results for the enrichment using KEGG database; B) GO enrichment results.
Inversion 16p11.2
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | Transcript | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|---|---|
| h_landuseshan300_preg_None | Land use (300m) | Building Environment | 16p11.2 | Mean | TC16000986.hg.1 | chr16:28390900-28437775 | EIF3CL;EIF3C | 0.0456787 | -0.5201213 |
| h_landuseshan300_preg_None | Land use (300m) | Building Environment | 16p11.2 | Mean | TC16000305.hg.1 | chr16:28699879-28747053 | EIF3C;EIF3CL | 0.0456787 | -0.5307593 |
| hs_as_m_Log2 | Arsenic | Metals | 16p11.2 | Mean | TC16000323.hg.1 | chr16:29495626-29495781 | DQ576952 | 0.0231242 | 0.0295406 |
| hs_cotinine_mcat_None | Cotinine | Tobacco Smoke | 16p11.2 | Mean | TC16000982.hg.1 | chr16:28009616-28009722 | RNU6-1241P | 0.0027473 | 0.2001604 |
| hs_globalsmok_m_None | Maternal smoking (active and ETS) | Tobacco Smoke | 16p11.2 | Mean | TC16000982.hg.1 | chr16:28009616-28009722 | RNU6-1241P | 0.0336587 | 0.1454652 |
Figure 17: Plot representations for the mean differentially expressed genes when inversion 16p11.2 interacts with exposome
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Inversion 17q21.31
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | Transcript | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC |
|---|---|---|---|---|---|---|---|---|---|
| hs_dmp_madj_Log2 | DMP | OP Pesticides | 17q21.31 | Mean | TC17001591.hg.1 | chr17:43100706-43138473 | DCAKD | 0.0487945 | -0.0272306 |
| hs_mnbp_madj_Log2 | MnBP | Phthalates | 17q21.31 | Mean | TC17001588.hg.1 | chr17:42982993-42992920 | GFAP;AK124465 | 0.0097880 | 0.0127936 |
| hs_zn_m_Log2 | Zn | Essential minerals | 17q21.31 | Mean | TC17000598.hg.1 | chr17:44450179-44500463 | NSFP1 | 0.0230469 | 0.4424501 |
| hs_zn_m_Log2 | Zn | Essential minerals | 17q21.31 | Mean | TC17001612.hg.1 | chr17:44363862-44439163 | ARL17A;ARL17B | 0.0230469 | 0.1752245 |
| hs_zn_m_Log2 | Zn | Essential minerals | 17q21.31 | Mean | TC17000600.hg.1 | chr17:44668035-44834830 | NSF;NSFP1 | 0.0230469 | 0.2429936 |
| hs_zn_m_Log2 | Zn | Essential minerals | 17q21.31 | Mean | TC17001613.hg.1 | chr17:44594068-44657088 | ARL17A | 0.0230469 | 0.1793518 |
| hs_zn_m_Log2 | Zn | Essential minerals | 17q21.31 | Mean | TC17001618.hg.1 | chr17:45110626-45137515 | ARL17 | 0.0230469 | 0.1908013 |
Figure 18: Plot representations for the mean differentially expressed genes when inversion 17q21.31 interacts with exposome (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 19: Plot representations for the mean differentially expressed genes when inversion 17q21.31 interacts with exposome (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
The differential analysis for methylome using the interaction between the inversion at 8p23.1 and exposome has revelaed the different mean methylation of the CpG sites that are displayed in Table 13. The enrichment results of the genes that contain these CpG sites are illustrated in Figure 20.The same has been implemented for inversion 16p11.2 and inversion 17q21.31 and the results are shown in Table 14 and Figure 21, and Table 15 and Figure 22, respectively.
Inversion 8p23.1
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | CpG | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | e3_alcpreg_yn_None | Alcohol intake | Lifestyle | 8p23.1 | Mean | cg12792075 | chr8:12244565 | FAM66A | 0.0053170 | -0.0656532 |
| 2 | e3_alcpreg_yn_None | Alcohol intake | Lifestyle | 8p23.1 | Mean | cg26670620 | chr8:12244544 | FAM66A | 0.0269268 | -0.0451624 |
| 12 | h_builtdens300_preg_Sqrt | Building density (300m) | Building Environment | 8p23.1 | Mean | cg02527252 | chr8:8178889 | PRAGMIN | 0.0444839 | 0.0000577 |
| 17 | h_folic_t1_None | Folic acid supplementation | Lifestyle | 8p23.1 | Mean | cg05753693 | chr8:10192930 | MSRA;MSRA;MSRA | 0.0098659 | 0.0124488 |
| 18 | h_folic_t1_None | Folic acid supplementation | Lifestyle | 8p23.1 | Mean | cg05267444 | chr8:11627012 | NEIL2;NEIL2;NEIL2;NEIL2 | 0.0283530 | 0.0149812 |
| 20 | h_fruit_preg_Ter | Fruits intake | Lifestyle | 8p23.1 | Mean | cg26670620 | chr8:12244544 | FAM66A | 0.0105750 | -0.0545383 |
| 21 | h_fruit_preg_Ter | Fruits intake | Lifestyle | 8p23.1 | Mean | cg12792075 | chr8:12244565 | FAM66A | 0.0105750 | -0.0696423 |
| 28 | h_no2_ratio_preg_Log | NO2 (preg) | Air Pollution | 8p23.1 | Mean | cg10613815 | chr8:11283299 | C8orf12;FAM167A | 0.0195207 | -0.0743761 |
| 42 | hs_k_m_Log2 | K | Essential minerals | 8p23.1 | Mean | cg06991484 | chr8:11540407 | 0.0388471 | -0.0738248 | |
| 46 | hs_mehhp_madj_Log2 | MEHHP | Phthalates | 8p23.1 | Mean | cg25925578 | chr8:8388047 | 0.0379205 | -0.0059698 | |
| 50 | hs_mn_m_Log2 | Manganese | Metals | 8p23.1 | Mean | cg14033944 | chr8:11627058 | NEIL2;NEIL2;NEIL2;NEIL2 | 0.0250874 | -0.0190271 |
| 65 | hs_pcb118_madj_Log2 | PCB 118 | OCs | 8p23.1 | Mean | cg11557530 | chr8:9911760 | MSRA;MSRA | 0.0001973 | -0.0104222 |
| 71 | hs_pfhxs_m_Log2 | PFHXS | PFASs | 8p23.1 | Mean | cg15537082 | chr8:9762300 | MIR124-1;LOC157627 | 0.0000224 | -0.0158329 |
| 78 | hs_pfna_m_Log2 | PFNA | PFASs | 8p23.1 | Mean | cg12792075 | chr8:12244565 | FAM66A | 0.0414350 | -0.0446670 |
| 82 | hs_pfos_m_Log2 | PFOS | PFASs | 8p23.1 | Mean | cg12792075 | chr8:12244565 | FAM66A | 0.0180689 | -0.0498219 |
| 88 | hs_prpa_madj_Log2 | PRPA | Phenols | 8p23.1 | Mean | cg22320962 | chr8:11560299 | GATA4 | 0.0033215 | 0.0058054 |
| 92 | hs_tl_mdich_None | Thallium | Metals | 8p23.1 | Mean | cg04815626 | chr8:9912509 | MSRA;MSRA | 0.0000004 | -0.0735296 |
Figure 20: Enrichment analysis for mean differentially methylated (MDM) genes using genotype-environment interaction for inversion 8p23.1
A) Results for the enrichment using DisGeNET database; B) GO enrichment results.
Inversion 16p11.2
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | CpG | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 30 | h_popdens_preg_Sqrt | Population density | Building Environment | 16p11.2 | Mean | cg26871973 | chr16:28565752 | CCDC101 | 0.0120178 | -0.0001515 |
| 66 | hs_pcb138_madj_Log2 | PCB 138 | OCs | 16p11.2 | Mean | cg04968132 | chr16:27560915 | GTF3C1;KIAA0556 | 0.0140690 | 0.0079734 |
| 67 | hs_pcb153_madj_Log2 | PCB 153 | OCs | 16p11.2 | Mean | cg04968132 | chr16:27560915 | GTF3C1;KIAA0556 | 0.0157908 | 0.0082358 |
| 68 | hs_pcb170_madj_Log2 | PCB 170 | OCs | 16p11.2 | Mean | cg07165637 | chr16:28102779 | 0.0399178 | -0.0058648 | |
| 70 | hs_pcb180_madj_Log2 | PCB 180 | OCs | 16p11.2 | Mean | cg04968132 | chr16:27560915 | GTF3C1;KIAA0556 | 0.0075376 | 0.0071593 |
| 72 | hs_pfhxs_m_Log2 | PFHXS | PFASs | 16p11.2 | Mean | cg00184016 | chr16:28833823 | ATXN2L;ATXN2L;ATXN2L;ATXN2L;ATXN2L | 0.0000217 | -0.0112217 |
| 73 | hs_pfhxs_m_Log2 | PFHXS | PFASs | 16p11.2 | Mean | cg09739165 | chr16:27637519 | KIAA0556 | 0.0033335 | -0.0103411 |
| 81 | hs_pfoa_m_Log2 | PFOA | PFASs | 16p11.2 | Mean | cg09629753 | chr16:29323721 | RUNDC2C | 0.0464170 | 0.0058505 |
| 89 | hs_prpa_madj_Log2 | PRPA | Phenols | 16p11.2 | Mean | cg12743398 | chr16:28609531 | SULT1A2 | 0.0067656 | 0.0081282 |
Figure 21: Enrichment analysis for mean differentially methylated (MDM) genes using genotype-environment interaction for inversion 16p11.2
A) Results for the enrichment using KEGG database; B) Results for the enrichment using DisGeNET database; C) GO enrichment results.
Inversion 17q21.31
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | CpG | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 6 | h_blueyn300_preg_None | Blue spaces (300 m) | Natural Spaces | 17q21.31 | Mean | cg11612592 | chr17:45266859 | CDC27;CDC27 | 0.0242926 | -0.0149990 |
| 14 | h_fastfood_preg_Ter | Fastfood intake | Lifestyle | 17q21.31 | Mean | cg03716233 | chr17:43128931 | DCAKD;DCAKD;DCAKD | 0.0025546 | 0.0168781 |
| 26 | h_landuseshan300_preg_None | Land use (300m) | Building Environment | 17q21.31 | Mean | cg13732302 | chr17:44222207 | KIAA1267 | 0.0294066 | -0.0448199 |
| 29 | h_pm10_ratio_preg_None | PM10 (preg) | Air Pollution | 17q21.31 | Mean | cg13001868 | chr17:43339223 | C17orf46;LOC100133991;LOC100133991 | 0.0001153 | -0.0011285 |
| 53 | hs_mo_m_Log2 | Molybdenum | Metals | 17q21.31 | Mean | cg03928887 | chr17:43200129 | PLCD3 | 0.0074031 | -0.0228002 |
Figure 22: Enrichment analysis for mean differentially methylated (MDM) genes using genotype-environment interaction for inversion 17q21.31
A) Results for the enrichment using KEGG database; B) GO enrichment results.
Table 16 summarizes the mediations of inversion - gene expression by the methylation of CpG sites.
| Inversion | Transcript | Location.Transcript | Symbol.Transcript | CpG | Location.CpG | Symbol.CpG | p.value.mediation | Prop.Mediated | p.value.prop.mediated | |
|---|---|---|---|---|---|---|---|---|---|---|
| 4 | 8p23.1 | TC08000087.hg.1 | chr8:11351510-11422113 | BLK | cg01383082 | chr8:11323474 | FAM167A | 0.000 | 0.2064627 | 0.000 |
| 264 | 8p23.1 | TC08000093.hg.1 | chr8:11653082-11696818 | FDFT1 | cg12568669 | chr8:11666485 | FDFT1 | 0.000 | 0.7909002 | 0.000 |
| 270 | 8p23.1 | TC08000093.hg.1 | chr8:11653082-11696818 | FDFT1 | cg12395012 | chr8:11607386 | GATA4 | 0.016 | 0.1526008 | 0.002 |
| 289 | 8p23.1 | TC08000093.hg.1 | chr8:11653082-11696818 | FDFT1 | cg02840367 | chr8:11660030 | FDFT1 | 0.001 | 0.4381081 | 0.000 |
| 363 | 8p23.1 | TC08000093.hg.1 | chr8:11653082-11696818 | FDFT1 | cg24387126 | chr8:11617293 | GATA4 | 0.043 | 0.1297336 | 0.000 |
| 530 | 8p23.1 | TC08000975.hg.1 | chr8:11278972-11324276 | FAM167A | cg01383082 | chr8:11323474 | FAM167A | 0.005 | 0.1929001 | 0.000 |
| 578 | 8p23.1 | TC08000975.hg.1 | chr8:11278972-11324276 | FAM167A | cg09528494 | chr8:11338675 | 0.000 | 0.2275709 | 0.000 | |
| 2894 | 8p23.1 | TC08000091.hg.1 | chr8:11627172-11644855 | NEIL2 | cg12568669 | chr8:11666485 | FDFT1 | 0.000 | 0.7808629 | 0.000 |
| 2898 | 8p23.1 | TC08000091.hg.1 | chr8:11627172-11644855 | NEIL2 | cg02711665 | chr8:11664728 | FDFT1 | 0.008 | 0.4051327 | 0.002 |
| 2919 | 8p23.1 | TC08000091.hg.1 | chr8:11627172-11644855 | NEIL2 | cg02840367 | chr8:11660030 | FDFT1 | 0.005 | 0.3826641 | 0.000 |
| 5577 | 16p11.2 | TC16000303.hg.1 | chr16:28565247-28603111 | CCDC101 | cg26624097 | chr16:28620651 | SULT1A1 | 0.000 | 0.1470226 | 0.000 |
| 5674 | 16p11.2 | TC16000986.hg.1 | chr16:28390900-28437775 | EIF3CL;EIF3C | cg09046979 | chr16:28333134 | SBK1 | 0.007 | 0.3444712 | 0.002 |
| 5724 | 16p11.2 | TC16000305.hg.1 | chr16:28699879-28747053 | EIF3C;EIF3CL | cg09046979 | chr16:28333134 | SBK1 | 0.008 | 0.3468888 | 0.004 |
| 5727 | 16p11.2 | TC16000305.hg.1 | chr16:28699879-28747053 | EIF3C;EIF3CL | cg26624097 | chr16:28620651 | SULT1A1 | 0.037 | 0.2344032 | 0.004 |
| 5834 | 16p11.2 | TC16000991.hg.1 | chr16:28616903-28634907 | SULT1A1 | cg01378222 | chr16:28622494 | SULT1A1 | 0.001 | 0.9542005 | 0.000 |
| 5840 | 16p11.2 | TC16000991.hg.1 | chr16:28616903-28634907 | SULT1A1 | cg26603685 | chr16:28620355 | SULT1A1 | 0.025 | 0.3621454 | 0.000 |
| 5883 | 16p11.2 | TC16002064.hg.1 | chr16:28477974-28503623 | CLN3 | cg03300649 | chr16:28504949 | APOB48R;CLN3 | 0.004 | 0.4945844 | 0.000 |
| 6040 | 16p11.2 | TC16000990.hg.1 | chr16:28603264-28608430 | SULT1A2 | cg26603685 | chr16:28620355 | SULT1A1 | 0.040 | 0.5651113 | 0.002 |
| 6276 | 17q21.31 | TC17001604.hg.1 | chr17:43590734-43593064 | AX747150;LRRC37A4P | cg12609785 | chr17:43660871 | 0.036 | 0.7639230 | 0.022 | |
| 6277 | 17q21.31 | TC17001604.hg.1 | chr17:43590734-43593064 | AX747150;LRRC37A4P | cg19832721 | chr17:44249866 | KIAA1267 | 0.025 | 0.8168810 | 0.008 |
The pregnancy exposures that have an impact on mean differentially methylated CpG sites are displayed in Table 17 (p<0.001).
| CpG | Location.CpG | Symbol.CpG | Exposure | Exposure.abreviation | p.value | FDR | |
|---|---|---|---|---|---|---|---|
| 195 | cg12940923 | chr8:10282607 | MSRA | h_cereal_preg_Ter | Cereals intake | 0.0000934 | 0.8191236 |
| 282 | cg01383082 | chr8:11323474 | FAM167A | h_abs_ratio_preg_Log | PMabsorbance (preg) | 0.0001804 | 0.8191236 |
| 846 | cg02319733 | chr8:10282549 | MSRA | h_cereal_preg_Ter | Cereals intake | 0.0000304 | 0.6167447 |
| 2164 | cg21915799 | chr8:10282809 | MSRA | h_ln_cat_preg_None | Traffic noise (night) | 0.0009921 | 0.8191236 |
| 2840 | cg01601443 | chr8:10581988 | SOX7 | hs_ddt_madj_Log2 | DDT | 0.0008052 | 0.8191236 |
| 2879 | cg01601443 | chr8:10581988 | SOX7 | hs_prpa_madj_Log2 | PRPA | 0.0003533 | 0.8191236 |
| 3569 | cg14257676 | chr8:10192642 | MSRA | h_temperature_t1_None | Temperature (t1) | 0.0001945 | 0.8191236 |
| 4093 | cg12792075 | chr8:12244565 | FAM66A | e3_alcpreg_yn_None | Alcohol intake | 0.0008227 | 0.8191236 |
| 4897 | cg02520399 | chr8:8168661 | hs_mecpp_madj_Log2 | MECPP | 0.0005269 | 0.8191236 | |
| 4899 | cg02520399 | chr8:8168661 | hs_mehp_madj_Log2 | MEHP | 0.0001409 | 0.8191236 | |
| 4900 | cg02520399 | chr8:8168661 | hs_meohp_madj_Log2 | MEOHP | 0.0001447 | 0.8191236 | |
| 5431 | cg06240162 | chr8:11142829 | MTMR9 | h_trafload_preg_pow1over3 | Road traffic load (100 m) | 0.0005749 | 0.8191236 |
| 5675 | cg10039590 | chr8:8859974 | ERI1 | e3_asmokyn_p_None | Active smoking (preg) | 0.0007744 | 0.8191236 |
| 6119 | cg16871763 | chr8:11537909 | hs_oxbe_madj_Log2 | OXBE | 0.0006213 | 0.8191236 | |
| 7277 | cg03059247 | chr8:11287657 | C8orf12;FAM167A | h_lden_cat_preg_None | Traffic noise (24h) | 0.0008778 | 0.8191236 |
| 7783 | cg01048752 | chr8:10001523 | MSRA | hs_meohp_madj_Log2 | MEOHP | 0.0009975 | 0.8191236 |
| 9810 | cg01716419 | chr8:11759663 | hs_co_m_Log2 | Cobalt | 0.0004052 | 0.8191236 | |
| 9878 | cg10613815 | chr8:11283299 | C8orf12;FAM167A | h_greenyn300_preg_None | Green spaces (300 m) | 0.0003378 | 0.8191236 |
| 12286 | cg07890238 | chr8:8182454 | PRAGMIN | h_clf_preg_Log | Water Chloroform | 0.0002960 | 0.8191236 |
| 12721 | cg02227026 | chr8:8173791 | hs_ohminp_madj_Log2 | OH-MiNP | 0.0009281 | 0.8191236 | |
| 13265 | cg07353006 | chr8:10405104 | hs_k_m_Log2 | K | 0.0004211 | 0.8191236 | |
| 13651 | cg03790427 | chr8:10530123 | C8orf74 | hs_ohminp_madj_Log2 | OH-MiNP | 0.0004012 | 0.8191236 |
| 13949 | cg04057858 | chr8:10383763 | T-SP1 | hs_trcs_madj_Log2 | TRCS | 0.0003413 | 0.8191236 |
| 15271 | cg11040268 | chr8:10447472 | h_fruit_preg_Ter | Fruits intake | 0.0000232 | 0.6167447 | |
| 17220 | cg16847396 | chr8:10489236 | RP1L1 | h_fdensity300_preg_Log | Facility density (300m) | 0.0004619 | 0.8191236 |
| 17223 | cg16847396 | chr8:10489236 | RP1L1 | h_frichness300_preg_None | Facility richness (300m) | 0.0003193 | 0.8191236 |
| 18281 | cg09052083 | chr8:10873619 | XKR6 | hs_dmp_madj_Log2 | DMP | 0.0007223 | 0.8191236 |
| 18375 | cg25083091 | chr8:10646690 | PINX1 | hs_dmtp_madj_Log2 | DMTP | 0.0006649 | 0.8191236 |
| 18854 | cg18127003 | chr8:11614472 | GATA4 | hs_mibp_madj_Log2 | MiBP | 0.0006986 | 0.8191236 |
| 21038 | cg04291970 | chr8:11226339 | C8orf12 | h_greenyn300_preg_None | Green spaces (300 m) | 0.0006052 | 0.8191236 |
| 21272 | cg17155499 | chr8:11644644 | NEIL2 | hs_mibp_madj_Log2 | MiBP | 0.0005205 | 0.8191236 |
| 21507 | cg08447380 | chr8:8185703 | PRAGMIN | h_legume_preg_Ter | Legumes intake | 0.0003115 | 0.8191236 |
| 22032 | cg09460231 | chr8:10736649 | hs_pfhxs_m_Log2 | PFHXS | 0.0008149 | 0.8191236 | |
| 22034 | cg09460231 | chr8:10736649 | hs_pfoa_m_Log2 | PFOA | 0.0003938 | 0.8191236 | |
| 24384 | cg27100760 | chr8:10708248 | h_frichness300_preg_None | Facility richness (300m) | 0.0003419 | 0.8191236 | |
| 25241 | cg00348858 | chr16:28858442 | TUFM | h_trafnear_preg_pow1over3 | Traffic density on nearest road | 0.0007075 | 0.8191236 |
| 26131 | cg02195680 | chr16:28519566 | IL27 | hs_tl_mdich_None | Thallium | 0.0005764 | 0.8191236 |
| 29238 | cg22968622 | chr17:43663579 | h_thm_preg_Log | Water THMs | 0.0009173 | 0.8191236 | |
| 29331 | cg12609785 | chr17:43660871 | h_thm_preg_Log | Water THMs | 0.0009579 | 0.8191236 | |
| 29424 | cg19832721 | chr17:44249866 | KIAA1267 | h_thm_preg_Log | Water THMs | 0.0009350 | 0.8191236 |
| 31637 | cg26855231 | chr17:44249543 | KIAA1267 | h_folic_t1_None | Folic acid supplementation | 0.0009498 | 0.8191236 |
| 32151 | cg02301815 | chr17:44249491 | KIAA1267 | hs_mepa_madj_Log2 | MEPA | 0.0005621 | 0.8191236 |
| 32281 | cg24203758 | chr17:43507018 | SH3D20 | h_clf_preg_Log | Water Chloroform | 0.0004701 | 0.8191236 |
| 32385 | cg13947929 | chr17:43863356 | CRHR1 | h_humidity_t1_None | Humidity (t1) | 0.0009737 | 0.8191236 |
| 32396 | cg13947929 | chr17:43863356 | CRHR1 | h_pm25_ratio_preg_None | PM2.5 (preg) | 0.0009218 | 0.8191236 |
| 33575 | cg08358943 | chr17:44889584 | WNT3 | e3_asmokyn_p_None | Active smoking (preg) | 0.0008655 | 0.8191236 |
| 37187 | cg11969213 | chr17:43324322 | LOC100133991;FMNL1 | hs_pcb138_madj_Log2 | PCB 138 | 0.0003928 | 0.8191236 |
| 38981 | cg16734549 | chr17:43488551 | ARHGAP27 | h_fastfood_preg_Ter | Fastfood intake | 0.0006613 | 0.8191236 |
| 40470 | cg12297030 | chr17:43662878 | h_fdensity300_preg_Log | Facility density (300m) | 0.0008056 | 0.8191236 |
The MDE genes and MDM CpG sites that are associated with human traits (p<0.01)are shown in Table 18 for inversion 8p23.1, in Table 19 for inversion 16p11.2, and in Table 20 for inversion 17q21.31.
| Inversion | Type_analysis | Feature | Diff | Location | Gene_Symbol | Type_phenotype | Phenotype | Phenotype_abrev | p.value | |
|---|---|---|---|---|---|---|---|---|---|---|
| 22 | 8p23.1 | Mean | TC08000099.hg.1 | G | chr8:12051976-12053789 | FAM85A | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0084915 |
| 26 | 8p23.1 | Mean | TC08000067.hg.1 | G | chr8:9046509-9060364 | BC017578 | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0091302 |
| 85 | 8p23.1 | Mean | cg12568669 | G | chr8:11666485 | FDFT1 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0031661 |
| 86 | 8p23.1 | Mean | cg12568669 | G | chr8:11666485 | FDFT1 | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0030220 |
| 89 | 8p23.1 | Mean | cg11548083 | G | chr8:10208156 | MSRA | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0072123 |
| 101 | 8p23.1 | Mean | cg02711665 | G | chr8:11664728 | FDFT1 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0071036 |
| 102 | 8p23.1 | Mean | cg02711665 | G | chr8:11664728 | FDFT1 | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0024376 |
| 161 | 8p23.1 | Mean | cg21725652 | G | chr8:10918152 | XKR6 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0012344 |
| 182 | 8p23.1 | Mean | cg03399933 | G | chr8:11205972 | TDH | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0061776 |
| 210 | 8p23.1 | Mean | cg04654363 | G | chr8:8581213 | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0089742 | |
| 230 | 8p23.1 | Mean | cg05753693 | G | chr8:10192930 | MSRA | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0055762 |
| 232 | 8p23.1 | Mean | cg05753693 | G | chr8:10192930 | MSRA | Obesity-related | e3_pi_None | Ponderal index | 0.0016517 |
| 246 | 8p23.1 | Mean | cg18303581 | G | chr8:8239485 | PRAGMIN | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0056206 |
| 254 | 8p23.1 | Mean | cg00074818 | G | chr8:8560427 | CLDN23 | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0079234 |
| 285 | 8p23.1 | Mean | cg17475643 | G | chr8:10261972 | MSRA | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0008020 |
| 286 | 8p23.1 | Mean | cg17475643 | G | chr8:10261972 | MSRA | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0001241 |
| 315 | 8p23.1 | Mean | cg18237548 | G | chr8:8860050 | ERI1 | Obesity-related | e3_bwc_None | Birth weight | 0.0068570 |
| 369 | 8p23.1 | Mean | cg18461678 | G | chr8:10472980 | RP1L1 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0036112 |
| 376 | 8p23.1 | Mean | cg12618270 | G | chr8:8667411 | MFHAS1 | Obesity-related | e3_pi_None | Ponderal index | 0.0061258 |
| 389 | 8p23.1 | Mean | cg03617420 | G | chr8:10916666 | XKR6 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0082839 |
| 515 | 8p23.1 | Mean | cg21088119 | G | chr8:11251471 | C8orf12 | Obesity-related | e3_bwc_None | Birth weight | 0.0068403 |
| 639 | 8p23.1 | Mean | cg22917652 | G | chr8:10283152 | MSRA | Obesity-related | e3_bwc_None | Birth weight | 0.0069590 |
| 645 | 8p23.1 | Mean | cg04413673 | G | chr8:10470278 | RP1L1 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0057046 |
| 694 | 8p23.1 | Mean | cg01619129 | G | chr8:10697017 | PINX1 | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0055125 |
| 857 | 8p23.1 | Mean | cg13519851 | G | chr8:10916560 | XKR6 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0040357 |
| 1006 | 8p23.1 | Mean | cg09500200 | G | chr8:9763033 | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0079069 | |
| 1131 | 8p23.1 | Mean | cg04015433 | G | chr8:8820844 | Obesity-related | e3_bwc_None | Birth weight | 0.0026194 | |
| 1170 | 8p23.1 | Mean | cg05753693 | G*E | chr8:10192930 | MSRA;MSRA;MSRA | Obesity-related | hs_totchol_c_None | Total Cholesterol | 0.0055762 |
| 1172 | 8p23.1 | Mean | cg05753693 | G*E | chr8:10192930 | MSRA;MSRA;MSRA | Obesity-related | e3_pi_None | Ponderal index | 0.0016517 |
| Inversion | Type_analysis | Feature | Diff | Location | Gene_Symbol | Type_phenotype | Phenotype | Phenotype_abrev | p.value | |
|---|---|---|---|---|---|---|---|---|---|---|
| 1212 | 16p11.2 | Mean | TC16000986.hg.1 | G | chr16:28390900-28437775 | EIF3CL;EIF3C | Obesity-related | hs_creatinine_c_None | Creatinine | 0.0034940 |
| 1213 | 16p11.2 | Mean | TC16000305.hg.1 | G | chr16:28699879-28747053 | EIF3C;EIF3CL | Obesity-related | hs_creatinine_c_None | Creatinine | 0.0041999 |
| 1231 | 16p11.2 | Mean | cg05683445 | G | chr16:28303182 | SBK1 | Obesity-related | hs_creatinine_c_None | Creatinine | 0.0097212 |
| 1274 | 16p11.2 | Mean | TC16000986.hg.1 | G*E | chr16:28390900-28437775 | EIF3CL;EIF3C | Obesity-related | hs_creatinine_c_None | Creatinine | 0.0034940 |
| 1275 | 16p11.2 | Mean | TC16000305.hg.1 | G*E | chr16:28699879-28747053 | EIF3C;EIF3CL | Obesity-related | hs_creatinine_c_None | Creatinine | 0.0041999 |
| 1286 | 16p11.2 | Mean | TC16000994.hg.1 | G | chr16:28853732-28857729 | TUFM;MIR4721 | Neurological | hs_nhitcolors1 | number of hits colors 1-back | 0.0010935 |
| 1316 | 16p11.2 | Mean | cg09046979 | G | chr16:28333134 | SBK1 | Neurological | hs_nhitcolors1 | number of hits colors 1-back | 0.0084540 |
| 1331 | 16p11.2 | Mean | cg00348858 | G | chr16:28858442 | TUFM | Neurological | hs_Esc_AD | NA | 0.0010217 |
| 1425 | 16p11.2 | Mean | cg04968132 | G*E | chr16:27560915 | GTF3C1;KIAA0556 | Neurological | hs_Esc_AD | NA | 0.0016233 |
| Inversion | Type_analysis | Feature | Diff | Location | Gene_Symbol | Type_phenotype | Phenotype | Phenotype_abrev | p.value | |
|---|---|---|---|---|---|---|---|---|---|---|
| 1479 | 17q21.31 | Mean | TC17001603.hg.1 | G | chr17:43578684-43597889 | LRRC37A4P | Neurological | hs_nhitcolors3 | number of hits colors 3-back | 0.0080836 |
| 1503 | 17q21.31 | Mean | cg05159804 | G | chr17:44343776 | Neurological | hs_nhitcolors3 | number of hits colors 3-back | 0.0051687 | |
| 1508 | 17q21.31 | Mean | cg05159804 | G | chr17:44343776 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0072184 | |
| 1516 | 17q21.31 | Mean | cg22968622 | G | chr17:43663579 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0023492 | |
| 1524 | 17q21.31 | Mean | cg12609785 | G | chr17:43660871 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0004113 | |
| 1528 | 17q21.31 | Mean | cg19832721 | G | chr17:44249866 | KIAA1267 | Neurological | hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 0.0097596 |
| 1532 | 17q21.31 | Mean | cg19832721 | G | chr17:44249866 | KIAA1267 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0085330 |
| 1534 | 17q21.31 | Mean | cg08113562 | G | chr17:43508428 | SH3D20 | Neurological | hs_nmisscolors1 | number of miss colors 1-back | 0.0082713 |
| 1535 | 17q21.31 | Mean | cg08113562 | G | chr17:43508428 | SH3D20 | Neurological | hs_nhitcolors3 | number of hits colors 3-back | 0.0095101 |
| 1548 | 17q21.31 | Mean | cg09764761 | G | chr17:44105544 | MAPT | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0038260 |
| 1550 | 17q21.31 | Mean | cg07368061 | G | chr17:44090862 | MAPT | Neurological | hs_nmisscolors1 | number of miss colors 1-back | 0.0036959 |
| 1551 | 17q21.31 | Mean | cg07368061 | G | chr17:44090862 | MAPT | Neurological | hs_nhitcolors3 | number of hits colors 3-back | 0.0036519 |
| 1552 | 17q21.31 | Mean | cg07368061 | G | chr17:44090862 | MAPT | Neurological | hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 0.0073823 |
| 1553 | 17q21.31 | Mean | cg07368061 | G | chr17:44090862 | MAPT | Neurological | hs_dcolors1 | detectability colors 1-back | 0.0063345 |
| 1558 | 17q21.31 | Mean | cg01341218 | G | chr17:43662625 | Neurological | hs_nmisscolors1 | number of miss colors 1-back | 0.0012065 | |
| 1561 | 17q21.31 | Mean | cg01341218 | G | chr17:43662625 | Neurological | hs_dcolors1 | detectability colors 1-back | 0.0046461 | |
| 1604 | 17q21.31 | Mean | cg22433210 | G | chr17:43662623 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0043393 | |
| 1621 | 17q21.31 | Mean | cg27503360 | G | chr17:43890749 | CRHR1 | Neurological | hs_nfacolors1 | number of false alarms colors 1-back | 0.0007558 |
| 1622 | 17q21.31 | Mean | cg27503360 | G | chr17:43890749 | CRHR1 | Neurological | hs_nmisscolors1 | number of miss colors 1-back | 0.0003260 |
| 1624 | 17q21.31 | Mean | cg27503360 | G | chr17:43890749 | CRHR1 | Neurological | hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 0.0000530 |
| 1625 | 17q21.31 | Mean | cg27503360 | G | chr17:43890749 | CRHR1 | Neurological | hs_dcolors1 | detectability colors 1-back | 0.0000575 |
| 1668 | 17q21.31 | Mean | cg08670715 | G | chr17:44341754 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0034266 | |
| 1687 | 17q21.31 | Mean | cg07368127 | G | chr17:44230994 | KIAA1267 | Neurological | hs_nhitcolors3 | number of hits colors 3-back | 0.0065754 |
| 1733 | 17q21.31 | Mean | cg24063856 | G | chr17:43863303 | CRHR1 | Neurological | hs_nfacolors1 | number of false alarms colors 1-back | 0.0014963 |
| 1736 | 17q21.31 | Mean | cg24063856 | G | chr17:43863303 | CRHR1 | Neurological | hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 0.0057192 |
| 1740 | 17q21.31 | Mean | cg24063856 | G | chr17:43863303 | CRHR1 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0065917 |
| 1785 | 17q21.31 | Mean | cg13947929 | G | chr17:43863356 | CRHR1 | Neurological | hs_dcolors1 | detectability colors 1-back | 0.0066662 |
| 1863 | 17q21.31 | Mean | cg06491244 | G | chr17:44851046 | WNT3 | Neurological | hs_nhitcolors3 | number of hits colors 3-back | 0.0038096 |
| 1883 | 17q21.31 | Mean | cg14260695 | G | chr17:43506184 | Neurological | hs_dnumeros3 | detectability numbers 3-back | 0.0006076 | |
| 1949 | 17q21.31 | Mean | cg00677574 | G | chr17:43221327 | ACBD4 | Neurological | hs_nfacolors1 | number of false alarms colors 1-back | 0.0096534 |
| 1952 | 17q21.31 | Mean | cg00677574 | G | chr17:43221327 | ACBD4 | Neurological | hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 0.0091555 |
| 2077 | 17q21.31 | Mean | cg10701640 | G | chr17:43249399 | Neurological | hs_nfacolors1 | number of false alarms colors 1-back | 0.0034319 | |
| 2080 | 17q21.31 | Mean | cg10701640 | G | chr17:43249399 | Neurological | hs_accuracy_colors1 | Percentage of correct responses (hits and correct rejections) colors 1-back | 0.0062625 | |
| 2196 | 17q21.31 | Mean | cg11969213 | G | chr17:43324322 | LOC100133991;FMNL1 | Neurological | hs_sum_non_domHand | Sum of the 2 trials nondominant hand | 0.0036855 |
| 2318 | 17q21.31 | Mean | cg10256219 | G | chr17:44270511 | Neurological | hs_nmisscolors1 | number of miss colors 1-back | 0.0033473 |
Inversion 8p23.1
The significant variance differentially methylated (VDM) genes for inversion 8p23.1 are shown in Table 21 and their distribution according to the inversion status is shown in Figure 23. The enrichment analysis of these genes has been performed and the results are presented in Figure 24.
| Inversion | Type_analysis | Transcript | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|
| 137 | 8p23.1 | Variance | TC08000093.hg.1 | chr8:11653082-11696818 | FDFT1 | dominant | 0.0218711 | -0.0271569 |
| 149 | 8p23.1 | Variance | TC08000087.hg.1 | chr8:11351510-11422113 | BLK | recessive | 0.0001042 | 0.0539874 |
| 1105 | 8p23.1 | Variance | TC08000975.hg.1 | chr8:11278972-11324276 | FAM167A | recessive | 0.0005347 | 0.0335541 |
Figure 23: Enrichment analysis results for variance differentially expressed (VDE) genes for inversion 8p23.1
The colour depends on the p-value adjusted and the size of the dot indicates the number of counts. A) Results using KEGG database; B) Results using DisGeNET database; c) Results using GO database.
Figure 24: Box-plot representation for the variance differentially expressed genes in inversion 8p23.1
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Inversion 16p11.2
In the case of the 16p11.2 region, Table 22 reveals the VDM genes and Figure 26 shows the distribution of their gene expression. The results of the enrichment analysis are displayed in Figure 25.
| Inversion | Type_analysis | Transcript | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|
| 1109 | 16p11.2 | Variance | TC16000994.hg.1 | chr16:28853732-28857729 | TUFM;MIR4721 | recessive | 0.0000000 | 0.0854456 |
| 1110 | 16p11.2 | Variance | TC16000303.hg.1 | chr16:28565247-28603111 | CCDC101 | recessive | 0.0055758 | 0.0414499 |
| 1112 | 16p11.2 | Variance | TC16000314.hg.1 | chr16:28986093-29002104 | LAT;SPNS1 | recessive | 0.0070762 | 0.0199462 |
Figure 25: Enrichment analysis results for variance differentially expressed (VDE) genes for inversion 16p11.2
The colour depends on the p-value adjusted and the size of the dot indicates the number of counts. A) Results using KEGG database; B) Results using DisGeNET database; c) Results using GO database.
Figure 26: Box-plot representation for the variance differentially expressed genes in inversion 16p11.2
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Inversion 17q21.31
The polymorphic inversion 17q21.31 changes the variance expression levels of the genes that appear in Table 23. Figures 28 and 29 illustrate the gene expression distribution of these genes. The enrichment analysis revealed the results present in Figure 27.
| Inversion | Type_analysis | Transcript | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|
| 125 | 17q21.31 | Variance | TC17000598.hg.1 | chr17:44450179-44500463 | NSFP1 | additive | 0.0000000 | -0.1340094 |
| 127 | 17q21.31 | Variance | TC17001608.hg.1 | chr17:43677491-43679748 | LOC644172 | additive | 0.0000000 | 0.0570190 |
| 129 | 17q21.31 | Variance | TC17000600.hg.1 | chr17:44668035-44834830 | NSF;NSFP1 | additive | 0.0000000 | -0.0734839 |
| 133 | 17q21.31 | Variance | TC17001603.hg.1 | chr17:43578684-43597889 | LRRC37A4P | additive | 0.0000009 | 0.0408847 |
| 135 | 17q21.31 | Variance | TC17001613.hg.1 | chr17:44594068-44657088 | ARL17A | additive | 0.0000018 | -0.0414159 |
| 136 | 17q21.31 | Variance | TC17001612.hg.1 | chr17:44363862-44439163 | ARL17A;ARL17B | additive | 0.0000018 | -0.0393735 |
| 186 | 17q21.31 | Variance | TC17000596.hg.1 | chr17:44270939-44274089 | KANSL1-AS1 | dominant | 0.0000351 | 0.0483197 |
| 140 | 17q21.31 | Variance | TC17001617.hg.1 | chr17:45098946-45099089 | LOC51326 | additive | 0.0123146 | -0.0272143 |
| 187 | 17q21.31 | Variance | TC17000599.hg.1 | chr17:44590076-44633016 | LRRC37A2 | dominant | 0.0013743 | -0.0432640 |
Figure 27: Enrichment analysis results for variance differentially expressed (VDE) genes for inversion 17q21.31
The colour depends on the p-value adjusted and the size of the dot indicates the number of counts. A) Results using KEGG database; B) Results using DisGeNET database; c) Results using GO database.
Figure 28: Box-plot representation for the variance differentially expressed genes in inversion 17q21.31 (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Figure 29: Box-plot representation for the variance differentially expressed genes in inversion 17q21.31 (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene, as well as the most significant model of inheritance with the corresponding p-value.
Inversion 8p23.1
The VDM CpG sites for inversion 8p23.1 are shown in Table 24 and their respective genes are enriched in functions revealed in Figure 30.
| Inversion | Type_analysis | CpG | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|
| 831 | 8p23.1 | Variance | cg26670620 | chr8:12244544 | FAM66A | dominant | 0.0000000 | -0.2169291 |
| 416 | 8p23.1 | Variance | cg23217680 | chr8:9029456 | additive | 0.0000000 | 0.0475589 | |
| 832 | 8p23.1 | Variance | cg12792075 | chr8:12244565 | FAM66A | dominant | 0.0000000 | -0.3205989 |
| 418 | 8p23.1 | Variance | cg07042170 | chr8:8831422 | additive | 0.0000000 | -0.0385251 | |
| 419 | 8p23.1 | Variance | cg01274122 | chr8:8749938 | MFHAS1 | additive | 0.0000000 | -0.0384226 |
| 420 | 8p23.1 | Variance | cg23361275 | chr8:8749919 | MFHAS1 | additive | 0.0000000 | -0.0434153 |
| 833 | 8p23.1 | Variance | cg02771117 | chr8:11279352 | FAM167A;C8orf12 | dominant | 0.0000000 | -0.1105227 |
| 422 | 8p23.1 | Variance | cg10220992 | chr8:11324327 | FAM167A | additive | 0.0000001 | 0.0295230 |
| 423 | 8p23.1 | Variance | cg02525722 | chr8:10404760 | additive | 0.0000004 | -0.0730879 | |
| 840 | 8p23.1 | Variance | cg10613815 | chr8:11283299 | C8orf12;FAM167A | dominant | 0.0000013 | -0.0967995 |
| 425 | 8p23.1 | Variance | cg26161004 | chr8:11413186 | BLK | additive | 0.0000045 | 0.0146637 |
| 1178 | 8p23.1 | Variance | cg00074818 | chr8:8560427 | CLDN23 | recessive | 0.0000046 | 0.0410251 |
| 427 | 8p23.1 | Variance | cg14702231 | chr8:11413234 | BLK | additive | 0.0000142 | 0.0186140 |
| 1181 | 8p23.1 | Variance | cg04025970 | chr8:8727303 | MFHAS1 | recessive | 0.0000100 | 0.0661478 |
| 1183 | 8p23.1 | Variance | cg17329886 | chr8:10513629 | RP1L1 | recessive | 0.0000211 | 0.0916817 |
| 1182 | 8p23.1 | Variance | cg26100214 | chr8:8580376 | recessive | 0.0000157 | 0.0394348 | |
| 1174 | 8p23.1 | Variance | cg02319733 | chr8:10282549 | MSRA | recessive | 0.0000001 | 0.0284070 |
| 432 | 8p23.1 | Variance | cg06671706 | chr8:8559999 | CLDN23 | additive | 0.0000851 | 0.0409551 |
| 433 | 8p23.1 | Variance | cg22799963 | chr8:11536778 | additive | 0.0002730 | 0.0158261 | |
| 434 | 8p23.1 | Variance | cg09768257 | chr8:11628346 | NEIL2 | additive | 0.0003564 | -0.0215618 |
| 837 | 8p23.1 | Variance | cg16038868 | chr8:10192619 | MSRA | dominant | 0.0000000 | -0.0320286 |
| 1176 | 8p23.1 | Variance | cg12940923 | chr8:10282607 | MSRA | recessive | 0.0000006 | 0.0491409 |
| 1191 | 8p23.1 | Variance | cg00115954 | chr8:11536551 | recessive | 0.0005374 | 0.0184790 | |
| 438 | 8p23.1 | Variance | cg08012294 | chr8:11723816 | CTSB | additive | 0.0011132 | -0.0212917 |
| 439 | 8p23.1 | Variance | cg00870242 | chr8:10530148 | C8orf74 | additive | 0.0013832 | -0.0099356 |
| 835 | 8p23.1 | Variance | cg02711665 | chr8:11664728 | FDFT1 | dominant | 0.0000000 | -0.0441326 |
| 848 | 8p23.1 | Variance | cg02840367 | chr8:11660030 | FDFT1 | dominant | 0.0004766 | -0.0610700 |
| 846 | 8p23.1 | Variance | cg14257676 | chr8:10192642 | MSRA | dominant | 0.0001814 | -0.0258372 |
| 1192 | 8p23.1 | Variance | cg00873037 | chr8:11626984 | NEIL2 | recessive | 0.0025521 | 0.0427238 |
| 444 | 8p23.1 | Variance | cg07761646 | chr8:7113462 | FAM90A13;FAM90A14 | additive | 0.0109105 | 0.0322748 |
| 445 | 8p23.1 | Variance | cg26966828 | chr8:10208257 | MSRA | additive | 0.0198429 | 0.0154769 |
| 836 | 8p23.1 | Variance | cg12568669 | chr8:11666485 | FDFT1 | dominant | 0.0000000 | -0.0788849 |
| 844 | 8p23.1 | Variance | cg01383082 | chr8:11323474 | FAM167A | dominant | 0.0001279 | -0.0338096 |
| 850 | 8p23.1 | Variance | cg13601595 | chr8:10468038 | RP1L1 | dominant | 0.0087112 | -0.0161153 |
| 853 | 8p23.1 | Variance | cg11302791 | chr8:10635419 | PINX1 | dominant | 0.0183353 | -0.0304665 |
| 854 | 8p23.1 | Variance | cg23584735 | chr8:10686021 | PINX1 | dominant | 0.0199375 | 0.0136403 |
| 855 | 8p23.1 | Variance | cg21701351 | chr8:11374773 | BLK | dominant | 0.0199375 | -0.0287833 |
| 857 | 8p23.1 | Variance | cg04541228 | chr8:11625883 | NEIL2 | dominant | 0.0203900 | -0.0196985 |
| 1171 | 8p23.1 | Variance | cg11548083 | chr8:10208156 | MSRA | recessive | 0.0000000 | 0.0522596 |
| 1184 | 8p23.1 | Variance | cg12395012 | chr8:11607386 | GATA4 | recessive | 0.0000271 | 0.0405963 |
| 1186 | 8p23.1 | Variance | cg15426459 | chr8:11813211 | recessive | 0.0000769 | 0.0406807 | |
| 1187 | 8p23.1 | Variance | cg11465442 | chr8:11832261 | DEFB136 | recessive | 0.0001216 | 0.0325567 |
| 1188 | 8p23.1 | Variance | cg06620390 | chr8:10192943 | MSRA | recessive | 0.0002587 | 0.0316767 |
| 1190 | 8p23.1 | Variance | cg08265495 | chr8:11212668 | TDH | recessive | 0.0004357 | 0.0435098 |
| 1193 | 8p23.1 | Variance | cg20449619 | chr8:10581784 | SOX7 | recessive | 0.0027532 | 0.0372796 |
| 1194 | 8p23.1 | Variance | cg03007522 | chr8:11562685 | GATA4 | recessive | 0.0033390 | 0.0206992 |
| 1196 | 8p23.1 | Variance | cg00629382 | chr8:10268916 | MSRA | recessive | 0.0052549 | 0.0212186 |
| 1201 | 8p23.1 | Variance | cg08841257 | chr8:10191002 | MSRA | recessive | 0.0117684 | 0.0287605 |
| 1204 | 8p23.1 | Variance | cg27598632 | chr8:7686204 | DEFB106B;DEFB106A | recessive | 0.0189025 | 0.0322949 |
| 1205 | 8p23.1 | Variance | cg08196601 | chr8:12869553 | C8orf79 | recessive | 0.0220116 | 0.0221846 |
Figure 30: Enrichment analysis results for variance differentially methylated (VDM) genes in inversion 8p23.1 using GO database
Inversion 16p11.2
The CpG sites that appear in Table 25 are VMD according to the 16p11.2 region status. Moreover, the enrichment of the genes that contain these CpG sites is presented in Figure 31.
| Inversion | Type_analysis | CpG | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|
| 1206 | 16p11.2 | Variance | cg09046979 | chr16:28333134 | SBK1 | recessive | 0.0000000 | 0.1680773 |
| 447 | 16p11.2 | Variance | cg12743398 | chr16:28609531 | SULT1A2 | additive | 0.0000000 | -0.0626002 |
| 448 | 16p11.2 | Variance | cg02358434 | chr16:28995271 | SPNS1;LAT | additive | 0.0145275 | 0.0094420 |
| 1207 | 16p11.2 | Variance | cg04270652 | chr16:28608894 | SULT1A2 | recessive | 0.0000000 | 0.0738242 |
| 1208 | 16p11.2 | Variance | cg27413008 | chr16:28519597 | IL27 | recessive | 0.0000000 | 0.0682448 |
| 1209 | 16p11.2 | Variance | cg26624097 | chr16:28620651 | SULT1A1 | recessive | 0.0001035 | 0.0621461 |
| 1210 | 16p11.2 | Variance | cg00348858 | chr16:28858442 | TUFM | recessive | 0.0001397 | 0.0351291 |
| 1211 | 16p11.2 | Variance | cg02896250 | chr16:28305533 | SBK1 | recessive | 0.0009491 | 0.0250289 |
| 1212 | 16p11.2 | Variance | cg26603685 | chr16:28620355 | SULT1A1 | recessive | 0.0031343 | 0.0325097 |
| 1213 | 16p11.2 | Variance | cg26792089 | chr16:28518200 | IL27 | recessive | 0.0062890 | 0.0169983 |
| 1214 | 16p11.2 | Variance | cg01378222 | chr16:28622494 | SULT1A1 | recessive | 0.0079658 | 0.0366399 |
Figure 31: Enrichment analysis results for variance differentially methylated (VDM) genes in inversion 16p11.2
A) Results using KEGG database; B) Results for the enrichment using DisGeNET database; C) Enrichment results using GO.
Inversion 17q21.31
Table 26 displays the CpG sites VMD depending on the inversion 17q21.31 genotype. Their respective genes have been used for an enrichment analysis which results are shown in Figure 32.
| Inversion | Type_analysis | CpG | Location | Gene_Symbol | model | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|
| 859 | 17q21.31 | Variance | cg22968622 | chr17:43663579 | dominant | 0.0000000 | 0.6499105 | |
| 450 | 17q21.31 | Variance | cg12609785 | chr17:43660871 | additive | 0.0000000 | 0.3727500 | |
| 451 | 17q21.31 | Variance | cg08113562 | chr17:43508428 | SH3D20 | additive | 0.0000000 | 0.1665435 |
| 1216 | 17q21.31 | Variance | cg05159804 | chr17:44343776 | recessive | 0.0000000 | 0.3924877 | |
| 1217 | 17q21.31 | Variance | cg19832721 | chr17:44249866 | KIAA1267 | recessive | 0.0000000 | 0.3943881 |
| 454 | 17q21.31 | Variance | cg02665463 | chr17:44657154 | ARL17A | additive | 0.0000000 | -0.1754514 |
| 1220 | 17q21.31 | Variance | cg01341218 | chr17:43662625 | recessive | 0.0000000 | 0.2161664 | |
| 1219 | 17q21.31 | Variance | cg09764761 | chr17:44105544 | MAPT | recessive | 0.0000000 | 0.2088788 |
| 1224 | 17q21.31 | Variance | cg07368061 | chr17:44090862 | MAPT | recessive | 0.0000000 | 0.1488632 |
| 1222 | 17q21.31 | Variance | cg05301556 | chr17:43971177 | MAPT;LOC100128977 | recessive | 0.0000000 | 0.1246551 |
| 1225 | 17q21.31 | Variance | cg22433210 | chr17:43662623 | recessive | 0.0000000 | 0.1676423 | |
| 1227 | 17q21.31 | Variance | cg01882395 | chr17:43717810 | C17orf69 | recessive | 0.0000000 | 0.1007474 |
| 1223 | 17q21.31 | Variance | cg03954353 | chr17:43715162 | C17orf69;MGC57346 | recessive | 0.0000000 | 0.1307532 |
| 1226 | 17q21.31 | Variance | cg00891649 | chr17:43972573 | MAPT;LOC100130148;LOC100128977 | recessive | 0.0000000 | 0.1218721 |
| 1230 | 17q21.31 | Variance | cg23659289 | chr17:43472725 | ARHGAP27 | recessive | 0.0000000 | 0.0429529 |
| 464 | 17q21.31 | Variance | cg03209459 | chr17:44604660 | ARL17A;LRRC37A2 | additive | 0.0004157 | -0.0345841 |
| 868 | 17q21.31 | Variance | cg05186793 | chr17:44235520 | KIAA1267 | dominant | 0.0000055 | -0.0485384 |
| 1231 | 17q21.31 | Variance | cg19943578 | chr17:43483527 | ARHGAP27 | recessive | 0.0000000 | 0.0427597 |
| 467 | 17q21.31 | Variance | cg13465858 | chr17:44204908 | KIAA1267 | additive | 0.0012275 | -0.0250799 |
| 468 | 17q21.31 | Variance | cg26250449 | chr17:44195907 | KIAA1267 | additive | 0.0075841 | -0.0223583 |
| 1233 | 17q21.31 | Variance | cg05772917 | chr17:44027251 | MAPT | recessive | 0.0000007 | 0.0429338 |
| 874 | 17q21.31 | Variance | cg19872068 | chr17:44250734 | KIAA1267 | dominant | 0.0075102 | -0.0177977 |
| 471 | 17q21.31 | Variance | cg00480298 | chr17:44068857 | MAPT | additive | 0.0136062 | 0.0204525 |
| 472 | 17q21.31 | Variance | cg25246246 | chr17:43503131 | ARHGAP27 | additive | 0.0170279 | -0.0096454 |
| 473 | 17q21.31 | Variance | cg03244997 | chr17:43503144 | ARHGAP27 | additive | 0.0188162 | -0.0085639 |
| 1238 | 17q21.31 | Variance | cg12798194 | chr17:43462791 | recessive | 0.0153532 | 0.0407342 | |
| 1232 | 17q21.31 | Variance | cg14374015 | chr17:44249569 | KIAA1267 | recessive | 0.0000006 | 0.0690504 |
| 1234 | 17q21.31 | Variance | cg27503360 | chr17:43890749 | CRHR1 | recessive | 0.0000008 | 0.0358867 |
| 1235 | 17q21.31 | Variance | cg21214508 | chr17:44248233 | KIAA1267 | recessive | 0.0049900 | 0.0508209 |
| 1236 | 17q21.31 | Variance | cg04491389 | chr17:44214771 | KIAA1267 | recessive | 0.0080905 | 0.0499102 |
| 1237 | 17q21.31 | Variance | cg18410271 | chr17:43472435 | ARHGAP27 | recessive | 0.0086483 | 0.0153128 |
Figure 32: Enrichment analysis results for variance differentially methylated (VDM) in inversion 17q21.31
A) Enrichment results using DisGeNET; B) Results for the enrichment using GO database.
The results of the VDA according to the genotype*exposure are displayed in Table 27 and Figures 33 and 34 for inverison 8p23.1, Table 28 and Figures 36 and 37 for inversion 16p11.2, and Table 29 and Figures 39 and 40 for inversion 17q21.31. The enrichment analysis results for the respective inversions are shown in Figures Figure 35, 38, and 41.
Inversion 8p23.1
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | Transcript | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 8 | h_ndvi100_preg_None | NDVI (100 m) | Natural Spaces | 8p23.1 | Variance | TC08001807.hg.1 | chr8:12435815-12438798 | AX747590 | 0.0112863 | -0.3297102 |
| 21 | hs_mecpp_madj_Log2 | MECPP | Phthalates | 8p23.1 | Variance | TC08000069.hg.1 | chr8:9413422-9639856 | TNKS | 0.0073701 | 0.0160530 |
| 27 | hs_meohp_madj_Log2 | MEOHP | Phthalates | 8p23.1 | Variance | TC08000069.hg.1 | chr8:9413422-9639856 | TNKS | 0.0085911 | 0.0140747 |
| 29 | hs_mep_madj_Log2 | MEP | Phthalates | 8p23.1 | Variance | TC08000987.hg.1 | chr8:11994677-11996586 | USP17L2 | 0.0472567 | 0.0149799 |
| 113 | hs_mnbp_madj_Log2 | MnBP | Phthalates | 8p23.1 | Variance | TC08000995.hg.1 | chr8:12282913-12293915 | FAM86B2;FAM86B1 | 0.0319913 | 0.0123571 |
| 114 | hs_oxominp_madj_Log2 | oxo-MiNP | Phthalates | 8p23.1 | Variance | TC08000056.hg.1 | chr8:8086092-8102387 | FAM86B3P | 0.0157725 | 0.0117731 |
| 116 | hs_pbde47_madj_Log2 | PBDE 47 | PBDEs | 8p23.1 | Variance | TC08000053.hg.1 | chr8:7812535-7866277 | FAM66E | 0.0455927 | 0.0122072 |
Figure 33: Plot representations for the variance differentially expressed genes when inversion 8p23.1 interacts with exposome (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 34: Plot representations for the variance differentially expressed genes when inversion 8p23.1 interacts with exposome (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 35: GO enrichment analysis for variance differentially expressed (VDE) genes using genotype-environment interaction for inversion 8p23.1
Inversion 16p11.2
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | Transcript | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 5 | h_landuseshan300_preg_None | Land use (300m) | Building Environment | 16p11.2 | Variance | TC16000303.hg.1 | chr16:28565247-28603111 | CCDC101 | 0.0411589 | -0.1501837 |
| 9 | h_pm25_ratio_preg_None | PM2.5 (preg) | Air Pollution | 16p11.2 | Variance | TC16000983.hg.1 | chr16:28109316-28223190 | XPO6 | 0.0405140 | -0.0076731 |
| 11 | h_walkability_mean_preg_None | Walkability | Building Environment | 16p11.2 | Variance | TC16000981.hg.1 | chr16:27798850-28074830 | GSG1L | 0.0229412 | -0.1381578 |
| 18 | hs_hcb_madj_Log2 | HCB | OCs | 16p11.2 | Variance | TC16000979.hg.1 | chr16:27471934-27561251 | GTF3C1 | 0.0013072 | 0.0273696 |
| 22 | hs_mehhp_madj_Log2 | MEHHP | Phthalates | 16p11.2 | Variance | TC16000303.hg.1 | chr16:28565247-28603111 | CCDC101 | 0.0178208 | 0.0207063 |
| 23 | hs_mehhp_madj_Log2 | MEHHP | Phthalates | 16p11.2 | Variance | TC16000304.hg.1 | chr16:28648975-28670003 | NPIPB8;NPIPL1 | 0.0432203 | 0.0140482 |
| 24 | hs_mehp_madj_Log2 | MEHP | Phthalates | 16p11.2 | Variance | TC16000303.hg.1 | chr16:28565247-28603111 | CCDC101 | 0.0246590 | 0.0207599 |
| 25 | hs_mehp_madj_Log2 | MEHP | Phthalates | 16p11.2 | Variance | TC16000986.hg.1 | chr16:28390900-28437775 | EIF3CL;EIF3C | 0.0372016 | 0.0446434 |
| 26 | hs_mehp_madj_Log2 | MEHP | Phthalates | 16p11.2 | Variance | TC16000305.hg.1 | chr16:28699879-28747053 | EIF3C;EIF3CL | 0.0372016 | 0.0451882 |
| 110 | hs_mibp_madj_Log2 | MiBP | Phthalates | 16p11.2 | Variance | TC16001479.hg.1 | chr16:29466412-29476301 | SLX1A-SULT1A3 | 0.0416940 | -0.0406769 |
| 111 | hs_mibp_madj_Log2 | MiBP | Phthalates | 16p11.2 | Variance | TC16000321.hg.1 | chr16:29465822-29476301 | SLX1B;SULT1A4;SULT1A3;SLX1B-SULT1A4;SLX1A;SLX1A-SULT1A3 | 0.0418980 | -0.0199711 |
| 118 | hs_pcb138_madj_Log2 | PCB 138 | OCs | 16p11.2 | Variance | TC16000979.hg.1 | chr16:27471934-27561251 | GTF3C1 | 0.0115090 | 0.0249389 |
Figure 36: Plot representations for the variance differentially expressed genes when inversion 16p11.2 interacts with exposome (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 37: Plot representations for the variance differentially expressed genes when inversion 16p11.2 interacts with exposome (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 38: GO enrichment analysis for variance differentially expressed (VDE) genes using genotype-environment interaction for inversion 16p11.2
Inversion 17q21.31
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | Transcript | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | h_clf_preg_Log | Water Chloroform | Water DBPs | 17q21.31 | Variance | TC17000581.hg.1 | chr17:43238264-43247406 | HEXIM2 | 0.0275387 | 0.0127057 |
| 2 | h_greenyn300_preg_None | Green spaces (300 m) | Natural Spaces | 17q21.31 | Variance | TC17002876.hg.1 | chr17:43861646-43913194 | CRHR1 | 0.0252909 | -0.0117903 |
| 14 | hs_cd_m_Log2 | Cadmium | Metals | 17q21.31 | Variance | TC17001599.hg.1 | chr17:43404732-43404863 | RNA5SP443 | 0.0451536 | -0.0347179 |
| 19 | hs_k_m_Log2 | K | Essential minerals | 17q21.31 | Variance | TC17000576.hg.1 | chr17:42977084-42982758 | CCDC103;FAM187A | 0.0075601 | 0.0678150 |
| 20 | hs_mbzp_madj_Log2 | MBzP | Phthalates | 17q21.31 | Variance | TC17001597.hg.1 | chr17:43331760-43339479 | SPATA32 | 0.0118166 | -0.0082706 |
| 117 | hs_oxominp_madj_Log2 | oxo-MiNP | Phthalates | 17q21.31 | Variance | TC17001588.hg.1 | chr17:42982993-42992920 | GFAP;AK124465 | 0.0301282 | 0.0056141 |
| 119 | hs_pcb138_madj_Log2 | PCB 138 | OCs | 17q21.31 | Variance | TC17000577.hg.1 | chr17:43138680-43186382 | NMT1 | 0.0476627 | -0.0222118 |
Figure 39: Plot representations for the variance differentially expressed genes when inversion 17q21.31 interacts with exposome (1)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 40: Plot representations for the variance differentially expressed genes when inversion 17q21.31 interacts with exposome (2)
There are shown the gene expression distributions for the different inversion genotypes: homozygous inverted (I/I), heterozygous (N/I), and homozygous non-inverted (N/N). On the top of each plot, it is displayed the name of the differentially expressed gene with the corresponding p-value.
Figure 41: GO enrichment analysis for variance differentially expressed (VDE) genes using genotype-environment interaction for inversion 17q21.31
The VDA for methylome using the interaction between the inversion at 8p23.1 and exposome has revelaed the different variance methylation of the CpG sites that are displayed in Table 30. The enrichment results of the genes that contain these CpG sites are illustrated in Figure 42.The same has been implemented for inversion 16p11.2 and inversion 17q21.31 and the results are shown in Table 31 and Figure 43, and Table 32 and Figure 44, respectively.
Inversion 8p23.1
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | CpG | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 3 | e3_alcpreg_yn_None | Alcohol intake | Lifestyle | 8p23.1 | Variance | cg23361275 | chr8:8749919 | MFHAS1 | 0.0015519 | 0.0820723 |
| 4 | e3_alcpreg_yn_None | Alcohol intake | Lifestyle | 8p23.1 | Variance | cg26670620 | chr8:12244544 | FAM66A | 0.0440143 | 0.1592449 |
| 5 | e3_asmokyn_p_None | Active smoking (preg) | Tobacco Smoke | 8p23.1 | Variance | cg10613815 | chr8:11283299 | C8orf12;FAM167A | 0.0388690 | 0.1487399 |
| 7 | h_blueyn300_preg_None | Blue spaces (300 m) | Natural Spaces | 8p23.1 | Variance | cg06952801 | chr8:10460235 | 0.0009129 | 0.2954732 | |
| 8 | h_blueyn300_preg_None | Blue spaces (300 m) | Natural Spaces | 8p23.1 | Variance | cg06032483 | chr8:9599206 | MIR597;TNKS | 0.0009129 | 0.0589440 |
| 9 | h_blueyn300_preg_None | Blue spaces (300 m) | Natural Spaces | 8p23.1 | Variance | cg02771117 | chr8:11279352 | FAM167A;C8orf12 | 0.0017817 | 0.2068133 |
| 13 | h_connind300_preg_Sqrt | Connectivity (300m) | Building Environment | 8p23.1 | Variance | cg08115957 | chr8:11838532 | DEFB135 | 0.0063598 | 0.0113932 |
| 15 | h_fastfood_preg_Ter | Fastfood intake | Lifestyle | 8p23.1 | Variance | cg08115957 | chr8:11838532 | DEFB135 | 0.0000083 | 0.2636294 |
| 16 | h_fdensity300_preg_Log | Facility density (300m) | Building Environment | 8p23.1 | Variance | cg18050997 | chr8:8176225 | PRAGMIN | 0.0137751 | 0.0385449 |
| 19 | h_folic_t1_None | Folic acid supplementation | Lifestyle | 8p23.1 | Variance | cg18718312 | chr8:11772119 | 0.0361960 | 0.0288110 | |
| 22 | h_fruit_preg_Ter | Fruits intake | Lifestyle | 8p23.1 | Variance | cg12792075 | chr8:12244565 | FAM66A | 0.0378623 | 0.2934985 |
| 23 | h_fruit_preg_Ter | Fruits intake | Lifestyle | 8p23.1 | Variance | cg10613815 | chr8:11283299 | C8orf12;FAM167A | 0.0378623 | 0.1375314 |
| 24 | h_greenyn300_preg_None | Green spaces (300 m) | Natural Spaces | 8p23.1 | Variance | cg10613815 | chr8:11283299 | C8orf12;FAM167A | 0.0002295 | -0.1706376 |
| 25 | h_humidity_t1_None | Humidity (t1) | Meteorological | 8p23.1 | Variance | cg21002223 | chr8:8747452 | MFHAS1 | 0.0302253 | -0.0035800 |
| 27 | h_legume_preg_Ter | Legumes intake | Lifestyle | 8p23.1 | Variance | cg22651416 | chr8:10643634 | PINX1 | 0.0325299 | -0.2103315 |
| 31 | h_trafload_preg_pow1over3 | Road traffic load (100 m) | Traffic | 8p23.1 | Variance | cg14143728 | chr8:9015622 | 0.0261573 | 0.0002424 | |
| 33 | h_walkability_mean_preg_None | Walkability | Building Environment | 8p23.1 | Variance | cg22008625 | chr8:10588386 | SOX7 | 0.0049448 | -0.2551065 |
| 34 | h_walkability_mean_preg_None | Walkability | Building Environment | 8p23.1 | Variance | cg08115957 | chr8:11838532 | DEFB135 | 0.0049448 | 0.6814331 |
| 35 | hs_cd_m_Log2 | Cadmium | Metals | 8p23.1 | Variance | cg01970784 | chr8:10191983 | MSRA;MSRA;MSRA | 0.0311820 | 0.0353690 |
| 36 | hs_co_m_Log2 | Cobalt | Metals | 8p23.1 | Variance | cg05753693 | chr8:10192930 | MSRA;MSRA;MSRA | 0.0216276 | -0.0240518 |
| 38 | hs_ddt_madj_Log2 | DDT | OCs | 8p23.1 | Variance | cg07340894 | chr8:8238774 | PRAGMIN | 0.0163915 | 0.0127018 |
| 39 | hs_ddt_madj_Log2 | DDT | OCs | 8p23.1 | Variance | cg24701369 | chr8:9535308 | TNKS | 0.0163915 | 0.0156689 |
| 40 | hs_dmp_madj_Log2 | DMP | OP Pesticides | 8p23.1 | Variance | cg01035616 | chr8:8235320 | PRAGMIN | 0.0142439 | 0.0216696 |
| 44 | hs_mbzp_madj_Log2 | MBzP | Phthalates | 8p23.1 | Variance | cg02519718 | chr8:11251277 | C8orf12 | 0.0314230 | 0.0117915 |
| 45 | hs_mecpp_madj_Log2 | MECPP | Phthalates | 8p23.1 | Variance | cg13601595 | chr8:10468038 | RP1L1 | 0.0005667 | 0.0245592 |
| 47 | hs_mehhp_madj_Log2 | MEHHP | Phthalates | 8p23.1 | Variance | cg13601595 | chr8:10468038 | RP1L1 | 0.0408846 | 0.0158393 |
| 48 | hs_mehhp_madj_Log2 | MEHHP | Phthalates | 8p23.1 | Variance | cg01383082 | chr8:11323474 | FAM167A | 0.0408846 | 0.0240998 |
| 49 | hs_meohp_madj_Log2 | MEOHP | Phthalates | 8p23.1 | Variance | cg13601595 | chr8:10468038 | RP1L1 | 0.0016208 | 0.0207452 |
| 51 | hs_mnbp_madj_Log2 | MnBP | Phthalates | 8p23.1 | Variance | cg26886855 | chr8:10694831 | PINX1 | 0.0113143 | 0.0178850 |
| 52 | hs_mnbp_madj_Log2 | MnBP | Phthalates | 8p23.1 | Variance | cg04009108 | chr8:7406299 | 0.0183098 | 0.0531549 | |
| 54 | hs_mo_m_Log2 | Molybdenum | Metals | 8p23.1 | Variance | cg17886471 | chr8:10339410 | 0.0013514 | 0.0949066 | |
| 55 | hs_mo_m_Log2 | Molybdenum | Metals | 8p23.1 | Variance | cg02192555 | chr8:9952926 | MSRA;MSRA;MSRA | 0.0246763 | -0.0876695 |
| 56 | hs_mo_m_Log2 | Molybdenum | Metals | 8p23.1 | Variance | cg10866298 | chr8:9760869 | LOC157627 | 0.0246763 | 0.0666171 |
| 57 | hs_mo_m_Log2 | Molybdenum | Metals | 8p23.1 | Variance | cg19882315 | chr8:11351846 | BLK;BLK | 0.0388953 | 0.0417569 |
| 60 | hs_oxbe_madj_Log2 | OXBE | Phenols | 8p23.1 | Variance | cg05870116 | chr8:8643280 | MFHAS1 | 0.0012419 | 0.0131867 |
| 61 | hs_oxominp_madj_Log2 | oxo-MiNP | Phthalates | 8p23.1 | Variance | cg02771117 | chr8:11279352 | FAM167A;C8orf12 | 0.0014269 | 0.0552437 |
| 63 | hs_pbde47_madj_Log2 | PBDE 47 | PBDEs | 8p23.1 | Variance | cg06952801 | chr8:10460235 | 0.0166467 | 0.0586597 | |
| 64 | hs_pbde47_madj_Log2 | PBDE 47 | PBDEs | 8p23.1 | Variance | cg02621357 | chr8:11296980 | FAM167A | 0.0467747 | 0.0139473 |
| 74 | hs_pfhxs_m_Log2 | PFHXS | PFASs | 8p23.1 | Variance | cg15537082 | chr8:9762300 | MIR124-1;LOC157627 | 0.0000000 | 0.1129251 |
| 79 | hs_pfna_m_Log2 | PFNA | PFASs | 8p23.1 | Variance | cg12792075 | chr8:12244565 | FAM66A | 0.0076081 | 0.2126663 |
| 80 | hs_pfna_m_Log2 | PFNA | PFASs | 8p23.1 | Variance | cg26670620 | chr8:12244544 | FAM66A | 0.0476208 | 0.1199816 |
| 83 | hs_pfos_m_Log2 | PFOS | PFASs | 8p23.1 | Variance | cg15537082 | chr8:9762300 | MIR124-1;LOC157627 | 0.0021212 | 0.0819322 |
| 84 | hs_pfos_m_Log2 | PFOS | PFASs | 8p23.1 | Variance | cg26670620 | chr8:12244544 | FAM66A | 0.0070993 | 0.1390674 |
| 85 | hs_pfos_m_Log2 | PFOS | PFASs | 8p23.1 | Variance | cg12792075 | chr8:12244565 | FAM66A | 0.0070993 | 0.2104820 |
| 86 | hs_pfos_m_Log2 | PFOS | PFASs | 8p23.1 | Variance | cg23045373 | chr8:11324048 | FAM167A | 0.0219238 | -0.0385984 |
| 87 | hs_pfunda_m_Log2 | PFUNDA | PFASs | 8p23.1 | Variance | cg00690195 | chr8:8915582 | 0.0015937 | 0.0339313 | |
| 90 | hs_prpa_madj_Log2 | PRPA | Phenols | 8p23.1 | Variance | cg11557530 | chr8:9911760 | MSRA;MSRA | 0.0400802 | 0.0075899 |
| 93 | hs_tl_mdich_None | Thallium | Metals | 8p23.1 | Variance | cg04815626 | chr8:9912509 | MSRA;MSRA | 0.0000000 | -0.3562787 |
| 94 | hs_tl_mdich_None | Thallium | Metals | 8p23.1 | Variance | cg14143728 | chr8:9015622 | 0.0000000 | -0.1703917 | |
| 95 | hs_tl_mdich_None | Thallium | Metals | 8p23.1 | Variance | cg01660034 | chr8:10259065 | MSRA;MSRA;MSRA | 0.0002209 | -0.2791986 |
| 96 | hs_tl_mdich_None | Thallium | Metals | 8p23.1 | Variance | cg02724490 | chr8:10488231 | RP1L1 | 0.0084887 | -0.0689882 |
| 99 | hs_trcs_madj_Log2 | TRCS | Phenols | 8p23.1 | Variance | cg12792075 | chr8:12244565 | FAM66A | 0.0090429 | -0.0446952 |
| 100 | hs_trcs_madj_Log2 | TRCS | Phenols | 8p23.1 | Variance | cg26670620 | chr8:12244544 | FAM66A | 0.0181742 | -0.0270895 |
Figure 42: Enrichment analysis for variance differentially methylated (VDM) genes using genotype-environment interaction for inversion 8p23.1
A) Results for the enrichment using KEGG database; B) Results for the enrichment using DisGeNET database; C) GO enrichment results.
Inversion 16p11.2
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | CpG | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 10 | h_blueyn300_preg_None | Blue spaces (300 m) | Natural Spaces | 16p11.2 | Variance | cg03328388 | chr16:28886581 | 0.0000617 | 0.1339691 | |
| 32 | h_trafnear_preg_pow1over3 | Traffic density on nearest road | Traffic | 16p11.2 | Variance | cg23797100 | chr16:28996053 | LAT;LAT;LAT;LAT | 0.0418998 | 0.0019718 |
| 41 | hs_dmtp_madj_Log2 | DMTP | OP Pesticides | 16p11.2 | Variance | cg04413090 | chr16:28302913 | SBK1 | 0.0457651 | 0.0124660 |
| 62 | hs_pb_m_Log2 | Lead | Metals | 16p11.2 | Variance | cg03328388 | chr16:28886581 | 0.0000000 | 0.1191119 | |
| 75 | hs_pfhxs_m_Log2 | PFHXS | PFASs | 16p11.2 | Variance | cg00184016 | chr16:28833823 | ATXN2L;ATXN2L;ATXN2L;ATXN2L;ATXN2L | 0.0000025 | 0.0413751 |
| 76 | hs_pfhxs_m_Log2 | PFHXS | PFASs | 16p11.2 | Variance | cg27027151 | chr16:27461638 | IL21R;IL21R;IL21R | 0.0005652 | 0.0213302 |
| 77 | hs_pfhxs_m_Log2 | PFHXS | PFASs | 16p11.2 | Variance | cg09739165 | chr16:27637519 | KIAA0556 | 0.0283103 | 0.0246679 |
| 91 | hs_prpa_madj_Log2 | PRPA | Phenols | 16p11.2 | Variance | cg26624097 | chr16:28620651 | SULT1A1;SULT1A1;SULT1A1;SULT1A1;SULT1A1 | 0.0071522 | -0.0135043 |
| 97 | hs_tl_mdich_None | Thallium | Metals | 16p11.2 | Variance | cg14791831 | chr16:28565295 | CCDC101;CCDC101 | 0.0071366 | -0.1086587 |
| 98 | hs_tl_mdich_None | Thallium | Metals | 16p11.2 | Variance | cg04395184 | chr16:28222866 | XPO6;XPO6 | 0.0098270 | -0.1232376 |
Figure 43: Enrichment analysis for variance differentially methylated (VDM) genes using genotype-environment interaction for inversion 16p11.2
A) Results for the enrichment using KEGG database; B) Results for the enrichment using DisGeNET database.
Inversion 17q21.31
| Exposure | Exposure_abrev | Family | Inversion | Type_analysis | CpG | Location | Gene_Symbol | adj.p.value | DiffLevene_logFC | |
|---|---|---|---|---|---|---|---|---|---|---|
| 11 | h_bro_preg_Log | Water Brominated THMs | Water DBPs | 17q21.31 | Variance | cg05772917 | chr17:44027251 | MAPT;MAPT;MAPT;MAPT;MAPT;MAPT | 0.0393166 | -0.0103595 |
| 37 | hs_co_m_Log2 | Cobalt | Metals | 17q21.31 | Variance | cg03928887 | chr17:43200129 | PLCD3 | 0.0000004 | 0.1100341 |
| 43 | hs_k_m_Log2 | K | Essential minerals | 17q21.31 | Variance | cg14178294 | chr17:43109690 | DCAKD;DCAKD | 0.0036910 | 0.0867444 |
| 58 | hs_mo_m_Log2 | Molybdenum | Metals | 17q21.31 | Variance | cg03928887 | chr17:43200129 | PLCD3 | 0.0000022 | 0.1533679 |
| 59 | hs_ohminp_madj_Log2 | OH-MiNP | Phthalates | 17q21.31 | Variance | cg18051346 | chr17:43238278 | HEXIM2;HEXIM2 | 0.0129852 | 0.0164671 |
| 69 | hs_pcb170_madj_Log2 | PCB 170 | OCs | 17q21.31 | Variance | cg04512931 | chr17:43341971 | LOC100133991;MAP3K14;LOC100133991 | 0.0020775 | 0.0256931 |
Figure 44: Enrichment analysis for variance differentially methylated (VDM) genes using genotype-environment interaction for inversion 17q21.31
A) Results for the enrichment using DisGeNET database; B) GO enrichment results.
Table 33 summarizes the mediations of inversion - gene expression by the methylation of CpG sites.
| Inversion | Transcript | Location.Transcript | Symbol.Transcript | CpG | Location.CpG | Symbol.CpG | p.value.mediation | Prop.Mediated | p.value.prop.mediated | |
|---|---|---|---|---|---|---|---|---|---|---|
| 27 | 8p23.1 | TC08000093.hg.1 | chr8:11653082-11696818 | FDFT1 | cg02840367 | chr8:11660030 | FDFT1 | 0.047 | 0.1889366 | 0.002 |
| 151 | 16p11.2 | TC16000994.hg.1 | chr16:28853732-28857729 | TUFM;MIR4721 | cg09046979 | chr16:28333134 | SBK1 | 0.005 | 0.1538787 | 0.010 |
The pregnancy exposures that have an impact (p<0.001) on variance differentially methylated CpG sites are displayed in Table 34.
| CpG | Location.CpG | Symbol.CpG | Exposure | Exposure.abreviation | p.value | FDR | |
|---|---|---|---|---|---|---|---|
| 87 | cg26670620 | chr8:12244544 | FAM66A | hs_pfos_m_Log2 | PFOS | 0.0003151 | 0.4283069 |
| 1222 | cg04025970 | chr8:8727303 | MFHAS1 | h_distinvnear1_preg_Log | Inverse distance to nearest road | 0.0003760 | 0.4283069 |
| 2139 | cg00115954 | chr8:11536551 | hs_zn_m_Log2 | Zn | 0.0001062 | 0.3924227 | |
| 3230 | cg11302791 | chr8:10635419 | PINX1 | hs_mibp_madj_Log2 | MiBP | 0.0004505 | 0.4283069 |
| 3840 | cg11465442 | chr8:11832261 | DEFB136 | h_ndvi100_preg_None | NDVI (100 m) | 0.0009214 | 0.7457064 |
| 4648 | cg08196601 | chr8:12869553 | C8orf79 | hs_tl_mdich_None | Thallium | 0.0003573 | 0.4283069 |
| 5659 | cg01378222 | chr16:28622494 | SULT1A1 | hs_pcb118_madj_Log2 | PCB 118 | 0.0000598 | 0.3924227 |
| 6653 | cg22433210 | chr17:43662623 | hs_ddt_madj_Log2 | DDT | 0.0003238 | 0.4283069 | |
| 6785 | cg01882395 | chr17:43717810 | C17orf69 | hs_prpa_madj_Log2 | PRPA | 0.0001376 | 0.3924227 |
| 6855 | cg03954353 | chr17:43715162 | C17orf69;MGC57346 | hs_mepa_madj_Log2 | MEPA | 0.0004236 | 0.4283069 |
The MDE genes and MDM CpG sites that are associated with human traits (p<0.01) are shown in Table 35 for inversion 8p23.1, and in Table 36 for inversion 17q21.31. There are not features associated with phenotypes for inversion 16p11.2.
| Inversion | Type_analysis | Feature | Diff | Location | Gene_Symbol | Type_phenotype | Phenotype | Phenotype_abrev | p.value | |
|---|---|---|---|---|---|---|---|---|---|---|
| 252 | 8p23.1 | Variance | cg06952801 | G*E | chr8:10460235 | Obesity-related | e3_pi_None | Ponderal index | 0.0031452 | |
| 269 | 8p23.1 | Variance | cg18718312 | G*E | chr8:11772119 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0027903 | |
| 281 | 8p23.1 | Variance | cg22651416 | G*E | chr8:10643634 | PINX1 | Obesity-related | hs_phospho_c_None | Phospholipids | 0.0058001 |
| Inversion | Type_analysis | Feature | Diff | Location | Gene_Symbol | Type_phenotype | Phenotype | Phenotype_abrev | p.value | |
|---|---|---|---|---|---|---|---|---|---|---|
| 694 | 17q21.31 | Variance | cg19943578 | G | chr17:43483527 | ARHGAP27 | Neurological | hs_accuracy_numeros3 | Percentage of correct responses (hits and correct rejections) numbers 3-back | 0.0019711 |
| 774 | 17q21.31 | Variance | cg27503360 | G | chr17:43890749 | CRHR1 | Neurological | hs_accuracy_numeros3 | Percentage of correct responses (hits and correct rejections) numbers 3-back | 0.0072822 |